903 results on '"Carretero, Oscar A."'
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2. A Novel Mechanism of Renal Microcirculation Regulation: Connecting Tubule-Glomerular Feedback
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Romero, Cesar A. and Carretero, Oscar A.
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- 2019
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3. Kinins and Cardiovascular Disease
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Carretero, Oscar A., Yang, Xiao-Ping, Rhaleb, Nour-Eddine, DeMello, Walmor C., editor, and Frohlich, Edward D., editor
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- 2010
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4. MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2–Dependent Pathway
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Cerniello, Flavia M., Carretero, Oscar A., Longo Carbajosa, Nadia A., Cerrato, Bruno D., Santos, Robson A., Grecco, Hernán E., and Gironacci, Mariela M.
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- 2017
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5. Kinins in the Heart
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Carretero, Oscar A., Conn, P. Michael, editor, and Share, Leonard, editor
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- 1999
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6. The molecular biology of the kallikrein-kinin system
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Carbini, Luis A., Scicli, A. Guillermo, Carretero, Oscar A., Lindpaintner, Klaus, editor, and Ganten, Detlev, editor
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- 1996
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7. Blood pressure homeostasis is maintained by a P311-TGF-β axis
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Badri, Kameswara Rao, Yue, Ming, Carretero, Oscar A., Aramgam, Sree Latha, Cao, Jun, Sharkady, Stephen, Kim, Gene H., Taylor, Gregory A., Byron, Kenneth L., and Schuger, Lucia
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Cellular proteins -- Properties ,Cellular control mechanisms -- Observations ,Blood pressure -- Regulation ,Health care industry - Abstract
P311 is an 8-kDa intracellular protein that is highly conserved across species and is expressed in the nervous system as well as in vascular and visceral smooth muscle cells. P311-null [...]
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- 2013
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8. N-acetyl-Ser-Asp-Lys-Pro inhibits interleukin-1β-mediated matrix metalloproteinase activation in cardiac fibroblasts
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Rhaleb, Nour-Eddine, Pokharel, Saraswati, Sharma, Umesh C., Peng, Hongmei, Peterson, Edward, Harding, Pamela, Yang, Xiao-Ping, and Carretero, Oscar A.
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- 2013
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9. N-Acetyl–seryl–aspartyl–lysyl–proline inhibits ET-1-induced collagen production by preserving Src homology 2-containing protein tyrosine phosphatase-2 activity in cardiac fibroblasts
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Peng, Hongmei, Carretero, Oscar A., Peterson, Edward L., Yang, Xiao-Ping, Santra, Kastuv, and Rhaleb, Nour-Eddine
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- 2012
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10. Local angiotensin II aggravates cardiac remodeling in hypertension
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Xu, Jiang, Carretero, Oscar A., Liao, Tang-Dong, Peng, Hongmei, Shesely, Edward G., Xu, Junxiao, Liu, Thomas S., Yang, James J., Reudelhuber, Timothy L., and Yang, Xiao-Ping
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Angiotensin -- Physiological aspects ,Angiotensin -- Genetic aspects ,Angiotensin -- Research ,Hypertension -- Risk factors ,Hypertension -- Genetic aspects ,Hypertension -- Research ,Heart enlargement -- Risk factors ,Heart enlargement -- Development and progression ,Heart enlargement -- Genetic aspects ,Heart enlargement -- Research ,Biological sciences - Abstract
Angiotensin II (ANG II) contributes to hypertension, cardiac hypertrophy, fibrosis, and dysfunction; however, it is difficult to separate the cardiac effect of ANG II from its hemodynamic action in vivo. To overcome the limitations, we used transgenic mice with cardiac-specific expression of a transgene fusion protein that releases ANG II from cardiomyocytes (Tg-ANG II) and treated them with deoxycorticosterone acetate (DOCA)-salt to suppress their systemic renin-angiotensin system. Using this unique model, we tested the hypothesis that cardiac ANG II, acting on the angiotensin type 1 receptor ([AT.sub.1]R), increases inflammation, oxidative stress, and apoptosis, accelerating cardiac hypertrophy and fibrosis. Male Tg-ANG II mice and their non-transgenic littermates (n-Tg) were uninephrectomized and divided into the following three groups: 1) vehicle-treated normotensive controls; 2) DOCA-salt; and 3) DOCA-salt + valsartan ([AT.sub.1]R blocker). Under basal conditions, systolic blood pressure (SBP) and cardiac phenotypes were similar between strains. In DOCA-salt hypertension, SBP increased similarly in both n-Tg and Tg-ANG II, and cardiac function did not differ between strains; however, Tg-ANG II had 1) greater ventricular hypertrophy as well as interstitial and perivascular fibrosis; 2) a higher number of deoxynucleotidyl-transferase-mediated dUTP nick end labeling-positive cells and infiltrating macrophages; 3) increased protein expression of NADPH oxidase 2 and transforming growth factor-[[beta].sub.1]; and 4) downregulation of phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase B (Akt) phosphorylation. Valsartan partially reversed these effects in Tg-ANG II but not in n-Tg. We conclude that, when hemodynamic loading conditions remain unchanged, cardiac ANG II does not alter heart size or cardiac functions. However, in animals with hypertension, cardiac ANG II, acting via [AT.sub.1]R, enhances inflammation, oxidative stress, and cell death (most likely via downregulation of PI 3-kinase and Akt), contributing to cardiac hypertrophy and fibrosis. inflammation; oxidative stress; cardiac hypertrophy; fibrosis doi: 10.1152/ajpheart.00538.2010.
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- 2010
11. Enhanced myogenic response in the afferent arteriole of spontaneously hypertensive rats
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Ren, YiLin, D'Ambrosio, Martin A., Liu, Ruisheng, Pagano, Patrick J., Garvin, Jeffrey L., and Carretero, Oscar A.
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Hypertension -- Health aspects ,Oxidases -- Health aspects ,Oxidases -- Research ,Myogenesis -- Research ,Biological sciences - Abstract
Spontaneously hypertensive rats (SHRs) have normal glomerular capillary pressure even though renal perfusion pressure is higher, suggesting that preglomerular vessels exhibit abnormally high resistance. This may be due to increased superoxide ([O.sup.-.sub.2]) production, which contributes to the vasoconstriction in hypertension. We tested the hypothesis that the myogenic response of the afferent arteriole (Af-Art) is exaggerated in SHRs because of increased levels of reactive oxygen species (ROS). Single Af-Arts were microdissected from kidneys of SHRs and Wistar-Kyoto (WKY) rats and microperfused in vitro. When perfusion pressure in the Af-Art was increased stepwise from 60 to 140 mmHg, the luminal diameter decreased by 8.4 [+ or -] 2.9% in WKY Af-Arts but fell by 29.3 [+ or -] 5.6% in SHR Af-Arts. To test whether ROS production is enhanced during myogenic response in SHRs, we measured chloromethyl-dichlorodihydrofluorescein diacetate acetyl ester (CM-[H.sub.2]DCFDA) florescence before and after increasing intraluminal pressure from 60 to 140 mmHg. Pressure-induced increases in ROS were fourfold greater in SHR Af-Arts compared with WKY Af-Arts (SHR, 48.0 [+ or -] 2.2%; and WKY, 12.2 [+ or -] 0.3%). To test whether [O.sup.-.sub.2] contributes to the myogenic response in SHRs, either the membrane-permeant [O.sup.-sub.2] scavenger Tempol or the nox2-based NADPH oxidase (NOX2) inhibitor gp91ds-tat were added to the Af-Art lumen and bath and the myogenic response was tested before and after treatment. Both Tempol ([10.sup.-4] M) and gp91ds-tat ([10.sup.-5] M) significantly attenuated the pressure-induced constriction in SHR Af-Arts but not in WKY Af-Arts. We conclude that 1) pressure-induced constriction is exaggerated in SHR Af-Arts, 2) NOX2-derived [O.sup.-.sub.2] may contribute to the enhanced myogenic response, and 3) [O.sup.-.sub.2] exerts little influence on the myogenic response under normotensive conditions. hypertension; superoxide doi: 10.1152/ajpheart.00537.2009.
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- 2010
12. Ac-SDKP inhibits transforming growth factor-[beta]1-induced differentiation of human cardiac fibroblasts into myofibroblasts
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Peng, Hongmei, Carretero, Oscar A., Peterson, Edward L., and Rhaleb, Nour-Eddine
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Muscle proteins -- Physiological aspects ,Transforming growth factors -- Physiological aspects ,Fibroblast growth factors -- Physiological aspects ,Collagen -- Properties ,Biological sciences - Abstract
N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibits collagen production and cell proliferation in cultured rat cardiac fibroblasts, but its effect on differentiation of fibroblasts into myofibroblasts is not known. High amounts of transforming growth factor-[beta]1 (TGF-[beta]1) have been found in fibrotic cardiac tissue. TGF-[beta]1 converts fibroblasts into myofibroblasts, which produce more extracellular matrix proteins than fibroblasts. We hypothesized that 1) Ac-SDKP inhibits TGF-[beta]1-induced differentiation of fibroblasts into myofibroblasts; and 2) this effect is mediated in part by blocking phosphorylation of small-mothers-against-decapentaplegic (Smad) 2 and extracellular signal-regulated kinase (ERK) 1/2. For this study, we used human fetal cardiac fibroblasts (HCFs), which do not spontaneously become myofibroblasts when cultured at low passages. We investigated the effect of Ac-SDKP on TGF-[beta]1-induced HCF transformation into myofibroblasts, Smad2 and ERK1/2 phosphorylation, Smad7 expression, cell proliferation, and collagen production. We also investigated TGF-[beta]1 production by HCFs stimulated with endothelin-1 (ET-1). As expected, HCFs treated with TGF-[beta]1 transformed into myofibroblasts as indicated by increased expression of [alpha]-smooth muscle actin and a higher proportion of the embryonic isoform of smooth muscle myosin compared with untreated cells. TGF-[beta]1 also increased Smad2 and ERK1/2 phosphorylation but did not affect Smad7 expression. In addition. TGF-[beta]1 stimulated HCF proliferation as indicated by an increase in mitochondrial dehydrogenase activity and collagen production (hydroxyproline assay). AcSDKP significantly inhibited all of the effects of TGF-[beta]1. It also inhibited ET-l-stimulated TGF-[beta]1 production. We concluded that Ac-SDKP markedly suppresses differentiation of human cardiac fibroblasts into myofibroblasts, probably by inhibiting the TGF-[beta]/ Smad/ERK1/2 signaling pathway, and thus mediating its anti-fibrotic effects. transforming growth factor-[beta]1; human cardiac myofibroblasts; N-acetyl-seryl-aspartyl-lysyl-proline; collagen; signal transduction; fibroblast differentiation doi: 10.1152/ajpheart.00464.2009.
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- 2010
13. Cross-talk between arterioles and tubules in the kidney
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Ren, YiLin, Garvin, Jeffrey L., Liu, Ruisheng, and Carretero, Oscar A.
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- 2009
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14. N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin
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Liu, Yun-He, D'Ambrosio, Martin, Liao, Tang-dong, Peng, Hongmei, Rhaleb, Nour-Eddine, Sharma, Umesh, Andre, Sabine, Gabius, Hans-J., and Carretero, Oscar A.
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Heart diseases -- Development and progression ,Lectins -- Properties ,Polypeptides -- Properties ,Cardiovascular system -- Research ,Biological sciences - Abstract
December Galectin-3 (Gal-3) is secreted by activated macrophages. In hypertension, Gal-3 is a marker for hypertrophic hearts prone to develop heart failure. Gal-3 infused in pericardial sac leads to cardiac inflammation, remodeling, and dysfunction. N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), a naturally occurring tetrapeptide, prevents and reverses inflammation and collagen deposition in the heart in hypertension and heart failure postmyocardial infarction. In the present study, we hypothesize that Ac-SDKP prevents Gal-3-induced cardiac inflammation, remodeling, and dysfunction, and these effects are mediated by the transforming growth factor (TGF)-[beta]/Smad3 signaling pathway. Adult male rats were divided into four groups and received the following intrapericardial infusion for 4 wk: 1) vehicle (saline, n = 8); 2) Ac-SDKP (800 [micro]g x [kg.sup.-1] x [day.sup.-1], n = 8); 3) Gal-3 (12 [micro]g/day, n = 7); and 4) Ac-SDKP + Gal-3 (n = 7). Left ventricular ejection fraction, cardiac output, and transmittal velocity were measured by echocardiography; inflammatory cell infiltration, cardiomyocyte hypertrophy, and collagen deposition in the heart by histological and immunohistochemical staining; and TGF-[beta] expression and Smad3 phosphorylation by Western blot. We found that, in the left ventricle, Gal-3 1) enhanced macrophage and mast cell infiltration, increased cardiac interstitial and perivascular fibrosis, and causes cardiac hypertrophy; 2) increased TGF-[beta] expression and Smad3 phosphorylation; and 3) decreased negative change in pressure over time response to isoproterenol challenge, ratio of early left ventricular filling phase to atrial contraction phase, and left ventricular ejection fraction. Ac-SDKP partially or completely prevented these effects. We conclude that Ac-SDKP prevents Gal-3-induced cardiac inflammation, fibrosis, hypertrophy, and dysfunction, possibly via inhibition of the TGF-[betya]/Smad3 signaling pathway. N-acetyl-seryl-aspartyl-lysyl-proline; cardiac dysfunction; fibrosis; inflammation
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- 2009
15. Angiotensin‐converting enzyme inhibitors increase anti‐fibrotic biomarkers in African Americans with left ventricular hypertrophy
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Romero, Cesar, primary, Mathew, Shobi, additional, Wasinski, Benjamin, additional, Reed, Brian, additional, Brody, Aaron, additional, Dawood, Rachelle, additional, Twiner, Michael J., additional, McNaughton, Candace D., additional, Fridman, Rafael, additional, Flack, John M., additional, Carretero, Oscar A., additional, and Levy, Phillip D., additional
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- 2021
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16. Heme oxygenase metabolites inhibit tubuloglomerular feedback (TGF)
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Ren, YiLin, D'Ambrosio, Martin A., Wang, Hong, Liu, Ruisheng, Garvin, Jeffrey L., and Carretero, Oscar A.
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Metabolites -- Properties ,Oxidases -- Properties ,Renal artery -- Properties ,Biological sciences - Abstract
Tubuloglomerular feedback (TGF) is the mechanism by which the macula densa (MD) senses increases in luminal NaCl concentration and sends a signal to constrict the afferent arteriole (Af-Art). The kidney expresses constitutively heine oxygenase-2 (HO-2) and low levels of HO-1. HOs release carbon monoxide (CO), biliverdin, and free iron. We hypothesized that renal HOs inhibit TGF via release of CO and biliverdin. Rabbit Af-Arts and attached MD were simultaneously microperfused in vitro. The TGF response was determined by measuring Af-Art diameter before and after increasing NaCl in the MD perfusate. When HO activity was inhibited by adding stannous mesoporphyrin (SnMP) to the MD perfusate, the TGF response increased from 2.1 [+ or -] 0.2 to 4.1 [+ or -] 0.4 [micro]m (P = 0.003, control vs. SnMP, n = 7). When a CO-releasing molecule, (CORM-3; 50 [micro]M), was added to the MD perfusate, the TGF response decreased by 41%, from 3.6 [+ or -] 0.3 to 2.1 [+ or -] 0.2 [micro]m (P < 0.001, control vs. CORM-3, n = 12). When CORM-3 at 100 [micro]M was added to the perfusate, it completely blocked the TGF response, from 4.2 [+ or -] 0.4 to -0.2 [+ or -] 0.3 [micro]m (P < 0.001, control vs. CORM-3, n = 6). When biliverdin was added to the perfusate, the TGF response decreased by 79%, from 3.4 [+ or -] 0.3 to 0.7 [+ or -] 0.4 [micro]m (P = 0.001, control vs. biliverdin, n = 6). The effects of SnMP and CORM-3 were not blocked by inhibition of nitric oxide synthase. We concluded that renal HO inhibits TGF probably via release of CO and biliverdin. HO regulation of TGF is a novel mechanism that could lead to a better understanding of the control of renal microcirculation and function. carbon monoxide; biliverdin; afferent arteriole; macula densa
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- 2008
17. Intracellular pH regulates superoxide production by the macula densa
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Liu, Ruisheng, Carretero, Oscar A., Ren, Yilin, Wang, Hong, and Garvin, Jeffrey L.
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Kidney glomerulus -- Properties ,Ion exchange -- Observations ,Hydrogen-ion concentration -- Measurement ,Hydrogen-ion concentration -- Methods ,Physiological research ,Biological sciences - Abstract
We hypothesized that elevated macula densa intracellular pH ([pH.sub.i]) during tubuloglomerular feedback enhances [O.sup.-.sub.2] production from NAD(P)H oxidase. Microdissected thick ascending limbs from rabbits with intact macula densa were cannulated and perfused with physiological saline. When luminal NaCl was switched from 10 to 80 mM, [O.sup.-.sub.2] production increased from 0.53 [+ or -] 0.09 to 2.62 [+ or -] 0.54 U/min (P < 0.01). To determine whether inhibiting the Na/H exchanger blocks [O.sup.-.sub.2] production, we used dimethyl amiloride (DMA) to block Na/H exchange. In the presence of DMA, [O.sup.-.sub.2] production induced by NaCl was blunted by 40%. To study the effect of [pH.sub.i] on [O.sup.-.sub.2] in intact macula densa cells, we measured [O.sup.-.sub.2] while pHi was changed by adjusting luminal pH. When the macula densa was perfused with 80 mM NaCl and the pH of the perfusate was switched to 6.8, 7.4, and 8.0, [O.sup.-.sub.2] production was significantly enhanced, but not at 10 mM NaCl. To ascertain the source of [O.sup.-.sub.2], we used the NAD(P)H oxidase inhibitor apocynin. In the presence of apocynin ([10.sup.-5] M), [O.sup.-.sub.2] production induced by elevating pHi was blocked. Finally, we measured the optimum pH for [O.sup.-.sub.2] production by the macula densa and found optimum extracellular pH is at 7.7 and optimum [pH.sub.] is ~8 for [O.sup.-.sub.2] production. We found that elevated [pH.sub.i] enhances [O.sup.-.sub.2] production from NAD(P)H oxidase induced by increasing luminal NaCl when the lumen is perfused with 80 mM NaCl, not 10 mM, and [O.sup.-.sub.2] production is pH sensitive, with an optimum [pH.sub.i] of 8. tubuloglomerular feedback; pH optimum; Na/H exchange; reactive oxygen species
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- 2008
18. Prevention of aortic fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in angiotensin II-induced hypertension
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Lin, Chun-Xia, Rhaleb, Nour-Eddine, Yang, Xiao-Ping, Liao, Tang-Dong, D'Ambrosio, Martin A., and Carretero, Oscar A.
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Fibrosis -- Prevention ,Hypertension -- Development and progression ,Protein kinases -- Properties ,Transforming growth factors -- Properties ,Arteriosclerosis -- Development and progression ,Biological sciences - Abstract
Fibrosis is an important component of large conduit artery disease in hypertension. The endogenous tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has anti-inflammatory and antifibrotic effects in the heart and kidney. However, it is not known whether Ac-SDKP has an anti-inflammatory and antifibrotic effect on conduit arteries such as the aorta. We hypothesize that in ANG II-induced hypertension Ac-SDKP prevents aortic fibrosis and that this effect is associated with decreased protein kinase C (PKC) activation, leading to reduced oxidative stress and inflammation and a decrease in the profibrotic cytokine transforming growth factor-[beta]1 (TGF-[beta]1) and phosphorylation of its second messenger Smad2. To test this hypothesis we used rats with ANG II-induced hypertension and treated them with either vehicle or Ac-SDKP. In this hypertensive model we found an increased collagen deposition and collagen type I and III mRNA expression in the aorta. These changes were associated with increased PKC activation, oxidative stress, intercellular adhesion molecule (ICAM)-1 mRNA expression, and macrophage infiltration. TGF-[beta]1 expression and Smad2 phosphorylation also increased. Ac-SDKP prevented these effects without decreasing blood pressure or aortic hypertrophy. Ac-SDKP also enhanced expression of inhibitory Smad7. These data indicate that in ANG II-induced hypertension Ac-SDKP has an aortic antifibrotic effect. This effect may be due in part to inhibition of PKC activation, which in turn could reduce oxidative stress, ICAM-1 expression, and macrophage infiltration. Part of the effect of Ac-SDKP could also be due to reduced expression of the profibrotic cytokine TGF-[beta]1 and inhibition of Smad2 phosphorylation. arteriosclerosis; vascular hypertrophy; inflammation; protein kinase C; transforming growth factor-[beta]1/Smad
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- 2008
19. Novel anti-inflammatory mechanisms of N-Acetyl-Ser-Asp-Lys-Pro in hypertension-induced target organ damage
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Sharma, Umesh, Rhaleb, Nour-Eddine, Pokharel, Saraswati, Harding, Pamela, Rasoul, Saman, Peng, Hongmei, and Carretero, Oscar A.
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Hypertension -- Complications and side effects ,Polypeptides -- Health aspects ,Polypeptides -- Physiological aspects ,Inflammation -- Prevention ,Hematopoietic stem cells -- Properties ,Macrophages -- Health aspects ,Macrophages -- Properties ,Biological sciences - Abstract
High blood pressure (HBP) is an important risk factor for cardiac, renal, and vascular dysfunction. Excess inflammation is the major pathogenic mechanism for HBP-induced target organ damage (TOD). N-acetyl-Ser-Asp-Lys-Pro (AcSDKP), a tetrapeptide specifically degraded by angiotensin converting enzyme (ACE), reduces inflammation, fibrosis, and TOD induced by HBP. Our hypothesis is that Ac-SDKP exerts its anti-inflammatory effects by inhibiting: 1) differentiation of bone marrow stem cells (BMSC) to macrophages, 2) activation and migration of macrophages, and 3) release of the proinflammatory cytokine TNF-[alpha] by activated macrophages. BMSC were freshly isolated and cultured in macrophage growth medium. Differentiation of murine BMSC to macrophages was analyzed by flow cytometry using F4/80 as a marker of macrophage maturation. Macrophage migration was measured in a modified Boyden chamber. TNF-[alpha] release by activated macrophages in culture was measured by ELISA. Myocardial macrophage activation in mice with ANG II-induced hypertension was studied by Western blotting of Mac-2 (galectin-3) protein. Interstitial collagen deposition was measured by picrosirius red staining. We found that Ac-SDKP (10 nM) reduced differentiation of cultured BMSC to mature macrophages by 24.5% [F4/80 positivity: 14.09 [+ or -] 1.06 mean fluorescent intensity for vehicle and 10.63 [+ or -] 0.35 for Ac-SDKP: P < 0.05]. Ac-SDKP also decreased galectin-3 and macrophage colony-stimulating factor-dependent macrophage migration. In addition, AcSDKP decreased secretion of TNF-[alpha] by macrophages stimulated with bacterial LPS. In mice with ANG II-induced hypertension, Ac-SDKP reduced expression of galectin-3, a protein produced by infiltrating macrophages in the myocardium, and interstitial collagen deposition. In conclusion, this study demonstrates that part of the anti-inflammatory effect of Ac-SDKP is due to its direct effect on BMSC and macrophage, inhibiting their differentiation, activation, and cytokine release. These effects explain some of the anti-inflammatory and antifibrotic properties of Ac-SDKP in hypertension. macrophages; inflammation: activation; angiotensin II
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- 2008
20. Role of cardiac overexpression of ANG II in the regulation of cardiac function and remodeling postmyocardial infarction
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Xu, Jiang, Carretero, Oscar A., Lin, Chun-Xia, Cavasin, Maria A., Shesely, Edward G., Yang, James J., Reudelhuber, Timothy L., and Yang, Xiao-Ping
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Cardiac pacing -- Research ,Heart enlargement -- Research ,Heart failure -- Research ,Angiotensin -- Research ,Heart cells -- Research ,Cardiovascular research ,Biological sciences - Abstract
ANG II has a clear role in development of cardiac hypertrophy, fibrosis, and dysfunction. It has been difficult, however, to determine whether these actions are direct or consequences of its systemic hemodynamic effects in vivo. To overcome this limitation, we used transgenic mice with cardiacspecific expression of a transgene fusion protein that releases ANG II from cardiomyocytes (Tg-ANG II-cardiac) without involvement of the systemic renin-angiotensin system and tested whether increased cardiac ANG II accelerates remodeling and dysfunction postmyocardial infarction (MI), whereas those mice show no evidence of cardiac hypertrophy under the basal condition. Male 12- to 14-wk-old Tg-ANG H-cardiac mice and their wild-type littermates (WT) were subjected to sham-MI or MI by ligating the left anterior descending coronary artery tbr 8 wk. Cardiac ANG II levels were ~10-fold higher in Tg-ANG H-cardiac mice than their WT, whereas ANG II levels in plasma and other tissues did not differ between strains. Systolic blood pressure and heart rate were similar between groups with or without MI. In sham-MI, Tg-ANG II-cardiac mice had increased collagen deposition and decreased capillary density. The differences between strains became more pronounced after MI. Although cardiac function was well preserved in the Tg-ANG II-cardiac mice with sham-MI, cardiac remodeling and dysfunction post-MI were more severe than WT. Our results demonstrate that, independent of systemic hemodynamic effects, cardiac ANG II may act locally in the heart, causing interstitial fibrosis in sham-MI and accelerating deterioration of cardiac dysfunction and remodeling post-MI. angiotensin II; myocardial infarction; heart failure; transgenic mice
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- 2007
21. Depolarization of the macula densa induces superoxide production via NAD(P)H oxidase
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Liu, Ruisheng, Garvin, Jeffrey L., Ren, YiLin, Pagano, Patrick J., and Carretero, Oscar A.
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Superoxide -- Properties ,Kidneys -- Physiological aspects ,Oxidases -- Properties ,Physiological research ,Biological sciences - Abstract
Superoxide ([O.sup.-.sub.2]) enhances tubuloglomerular feedback by scavenging nitric oxide at the macula densa. However, the singling pathway of [O.sup.-.sub.2] production in the macula densa is not known. We hypothesized that the increase in tubular NaCl concentration that initiates tubuloglomerular feedback induces [O.sup.-.sub.2] production by the macula densa via NAD(P)H oxidase, which is activated by macula densa depolarization. We isolated and microperfused the thick ascending limb of the loop of Henle and attached macula densa in rabbits. A fluorescent dye, dihydroethidium, was used to detect [O.sup.-.sub.2] production at the macula densa. When luminal NaCl was switched from 10 to 80 mM, a situation of initiating maximum tubuloglomerular feedback response, [O.sup.-.sub.2] production significantly increased. To make sure that the shifts in the oxyethidium/dihydroethidium ratio were due to changes in [O.sup.-.sub.2], we used tempol ([10.sup.-4] M), a stable membrane-permeant superoxide dismutase mimetic. With tempol present, when we switched from 10 to 80 mM NaCl, the increase in oxyethidium/dihydroethidium ratio was blocked. To determine the source of [O.sup.-.sub.2], we used the NAD(P)H oxidase inhibitor apocynin. When luminal NaCl was switched from 10 to 80 mM in the presence of apocynin, [O.sup.-.sub.2] production was inhibited by 80%. To see whether the effect of increasing luminal NaCl involves Na-K-2Cl cotransporters, we inhibited them with furosemide. When luminal NaCl was switched from 10 to 80 mM in the presence of furosemide, [O.sup.-.sub.2] production was blocked. To test whether depolarization of the macula densa induces [O.sup.-.sub.2] production, we artificially induced depolarization by adding valinomycin ([10.sup.-6] M) and 25 mM KCl to the luminal perfusate. Depolarization alone significantly increases [O.sup.-.sub.2] production. We conclude that increasing luminal NaC1 induces [O.sup.-.sub.2] production during tubuloglomerular feedback. [O.sup.-.sub.2] generated by the macula densa is primarily derived from NAD(P)H oxidase and is induced by depolarization. tubuloglomerular feedback doi:10.1152/ajprenal.00515.2006
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- 2007
22. Characterization and localization of Ac-SDKP receptor binding sites using [sup.125]I-labeled Hpp-Aca-SDKP in rat cardiac fibroblasts
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Zhuo, Jia L., Carretero, Oscar A., Peng, Hongmei, Li, Xiao C., Regoli, Domenico, Neugebauer, Witold, and Rhaleb, Nour-Eddine
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Rats -- Physiological aspects ,Rattus -- Physiological aspects ,Autoradiography -- Usage ,Cell proliferation -- Research ,Biological sciences - Abstract
We have shown that the tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibited endothelin-1 (ET-1)-induced cell proliferation and collagen synthesis in cultured rat cardiac fibroblasts (CFs) and reduced left ventricle collagen deposition in rats with aldosterone (salt)- and ANG II-induced hypertension. However, it is not known whether these effects are mediated by receptor binding sites specific for Ac-SDKP. We hypothesized that Ac-SDKP exerts antifibrotic effects by binding to specific receptor sites in cultured rat CFs, which mediate the inhibitory effects of Ac-SDKP on ET-1-stimulated collagen synthesis. Ac-SDKP binding sites in rat CFs and hearts were characterized by a specific radioligand, [sup.125]I-labeled 3-(p-hydroxyphenyl)-propionic acid (or desaminotyrosine) (Hpp)-Aca-SDKP, a biologically active analog of Ac-SDKP. [sup.125]I-labeled Hpp-Aca-SDKP bound to rat CFs and fractionated membranes with similar affinities and specificity in a concentration- and time-dependent fashion. Scatchard plot analyses revealed a single class of high-affinity Hpp-Aca-SDKP binding sites (maximal binding: 1,704 [+ or -] 198 fmol/mg protein; dissociation constant: 3.3 [+ or -] 0.6 nM). [sup.125]I-labeled Hpp-Aca-SDKP binding in CFs was displaced by unlabeled native peptide Ac-SDKP (inhibition constant: 0.69 [+ or -] 0.15 nM) and the analog Hpp-Aca-SDKP (inhibition constant: 10.4 [+ or -] 0.2 nM) but not the unrelated peptide ANG II or ET-1 (10 [micro]M). In vitro, both Ac-SDKP and Hpp-Aca-SDKP inhibited ET-1-stimulated collagen synthesis in CFs in a dose-dependent fashion, reaching a maximal effect at 1 nM (control: 7.5 [+ or -] 0.4, ET-1: 19.9 [+ or -] 1.2, ET-1+SDKP: 7.7 [+ or -] 0.4, ET-1+Hpp-Aca-SDKP: 9.7 [+ or -] 0.1 [micro]g/mg protein; P < 0.001). Ac-SDKP also significantly attenuated ET-1-induced increases in intracellular calcium and MAPK ERK1/2 phosphorylation in CFs. In the rat heart, in vitro autoradiography revealed specific [sup.125]I-labeled Hpp-Aca-SDKP binding throughout the myocardium, primarily interstitially. We believe that these results demonstrate for the first time that Hpp-Aca-SDKP is a functional ligand specific for Ac-SDKP receptor binding sites and that both Ac-SDKP and Hpp-Aca-SDKP exert antifibrotic effects by binding to Ac-SDKP receptors in rat CFs. collagen synthesis; heart; autoradiography; receptor
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- 2007
23. A[T.sub.1] receptor-mediated accumulation of extracellular angiotensin II in proximal tubule cells: role of cytoskeleton microtubules and tyrosine phosphatases
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Li, Xiao C., Carretero, Oscar A., Navar, L. Gabriel, and Zhuo, Jia L.
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Endocytosis -- Research ,Angiotensin -- Receptors ,Angiotensin -- Research ,Biological sciences - Abstract
Long-term angiotensin II (ANG II) administration is associated with increased ANG II accumulation in the kidney, but intrarenal compartment(s) involved in this response remains to be determined. We tested the hypothesis that 1) extracellular ANG H is taken up by proximal tubule cells (PTCs) through A[T.sub.1] receptor-mediated endocytosis, 2) this process is regulated by cytoskeleton microtubule- and tyrosine phosphatase[dependent mechanisms, and 3) A[T.sub.1] receptor-mediated endocytosis of ANG H has a functional relevance by modulating intracellular cAMP signaling. In cultured PTCs, [[sup.125]I]Tyr-labeled ANG II and fluorescein labeled-ANG II were internalized in a time-dependent manner and 'colocalized with the endosome marker Alexa Fluor 594-transferrin. Endocytosis of extracellular ANG II was inhibited by the A[T.sub.1] receptor iblocker losartan (16.5 [+ or -] 4.6%, P < 0.01 vs. ANG II, 78.3 [+ or -] 6.2%) and by the tyrosine phosphatase inhibitor phenylarsine oxide (PAO; 30.0 [+ or -] 3.5%, P < 0.05 vs. ANG II). Intracellular ANG II levels were increased by ~58% (basal, 229.8 [+ or -] 11.4 vs. ANG II, 361.3 [+ or -] 11.8 pg ANG II/mg protein, P < 0.01), and the responses were blocked by losartan (P < '0.01), the cytoskeleton microtubule inhibitor colchicine (P < 0.05), and PAO (P < 0.01), whereas depletion of clathrin-coated pits with hyperosmotic sucrose had no effect (356.1 [+ or -] 25.5 pg ANG II/mg protein, not 'significant). ANG II accumulation was associated with significant inhibition of both basal (control, 15.5 [+ or -] 2.8 vs. ANG II, 9.1 [+ or -] 2.4 pmol/mg protein, P < 0.05) and forskolin-stimulated cAMP signaling (forskolin, 68.7 [+ or -] 8.6 vs. forskolin + ANG II, 42.8 [+ or -] 13.8 pmol/mg protein, P < 0.01). These effects were blocked by losartan and PAO. We conclude that extracellular ANG II is internalized in PTCs through A[T.sub.1] receptor-mediated endocytosis and that internalized ANG II may play a functional role in proximal tubule cells by inhibiting intracellular cAMP signaling. kidney; receptor-mediated endocytosis doi:10.1152/ajprenal.00405.2005
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- 2006
24. Intracellular ANG II induces cytosolic [Ca.sup.2+] mobilization by stimulating intracellular A[T.sub.1] receptors in proximal tubule cells
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Zhuo, Jia L., Li, Xiao C., Garvin, Jeffrey L., Navar, L. Gabriel, and Carretero, Oscar A.
- Subjects
Calcium, Dietary -- Properties ,Calcium, Dietary -- Analysis ,Endocytosis -- Research ,Kidneys -- Research ,Biological sciences - Abstract
Intracellular ANG II induces biological effects in nonrenal cells, but it is not known whether it plays a physiological role in renal proximal tubule cells (PTCs). PTCs express angiotensinogen, renin, and angiotensin-converting enzyme mRNAs, suggesting the presence of high levels of intracellular ANG II. We determined if microinjection of ANG II directly in single PTCs increases intracellular calcium concentration ([[[Ca.sup.2+]].sub.i]) and, if so, elucidated the cellular mechanisms involved. Changes in [[Ca.sup.2+]]i responses were studied by fluorescence imaging using the [Ca.sup.2+] indicator fluo 3. ANG II (1 nM) was microinjected directly in the cells, whereas cell-surface angiotensin type 1 (A[T.sub.1]) receptors were blocked by losartan (10 [micro]M). When ANG II (1 nM) was added to the perfusate, there was a marked increase in [[[Ca.sup.2+]].sub.i] that was blocked by extracellular losartan. With losartan in the perfusate, intracellular microinjection of ANG II elicited a robust increase in cytoplasmic [[[Ca.sup.2+]].sub.i] that peaked at 30 s (basal: 2.2 [+ or -] 0.3 vs. ANG II: 14.9 [+ or -] 0.4 relative fluorescence units; P < 0.01). Chelation of extracellular [Ca.sup.2+] with EGTA (2 mM) did not alter microinjected ANG II-induced [[[Ca.sup.2+].sub.i] responses ([Ca.sup.2+] free + ANG II: 12.3 [+ or -] 2.6 relative fluorescence units, not significant vs. ANG II); however, pretreatment with thapsigargin to deplete intracellular [Ca.sup.2+] stores or with U-73122 to inhibit phospholipase C (1 [micro]M each) markedly attenuated microinjected ANG II-induced [[[Ca.sup.2+].sub.i] responses. Combined microinjection of ANG II and losartan abolished [[[Ca.sup.2+]].sub.i] responses, whereas a combination of ANG II and PD-123319 had no effect. These data demonstrate for the first time that direct microinjection of ANG II in single PTCs increases [[[Ca.sup.2+]].sub.i] by stimulating intracellular A[T.sub.1] receptors and releases [Ca.sup.2+] from intracellular stores, suggesting that intracellular ANG II may play a physiological role in PTC function. intracellular calcium; kidney: microinjection; proximal tubules; receptor-mediated endocytosis
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- 2006
25. Role of inducible nitric oxide synthase in cardiac function and remodeling in mice with heart failure due to myocardial infarction
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Liu, Yun-He, Carretero, Oscar A., Cingolani, Oscar H., Liao, Tang-Dong, Sun, Ying, Xu, Jiang, Li, Lisa Y., Pagano, Patrick J., Yang, James J., and Yang, Xiao-Ping
- Subjects
Nitric oxide -- Research ,Heart attack -- Health aspects ,Heart attack -- Research ,Heart beat -- Observations ,Biological sciences - Abstract
Using inducible nitric oxide (NO) synthase (iNOS) knockout mice (iNO[S.sup.-/-]), we tested the hypotheses that 1) lack of iNOS attenuates cardiac remodeling and dysfunction and improves cardiac reserve postmyocardial infarction (MI), an effect that is partially mediated by reduction of oxidative stress due to reduced interaction between NO and reactive oxygen species (ROS); and 2) the cardioprotection afforded by iNOS deletion is eliminated by [N.sup.[omega]]-nitro-L-arginine methyl ester (L-NAME) due to inhibition of endothelial NOS (eNOS) and neuronal NOS (nNOS). MI was induced by ligating the left anterior descending coronary artery. Male iNO[S.sup.-/-] mice and wild-type controls (WT, C57BL/6J) were divided into sham MI, MI+vehicle, and MI + l-NAME (100 mg.[kg.sup.-1]*[day.sup.-1] in drinking water for 8 wk). Cardiac function was evaluated by echocardiography. Left ventricular (LV) maximum rate of rise of ventricular pressure divided by pressure at the moment such maximum occurs (dP/dt/instant pressure) in response to isoproterenol (100 ng.[kg.sup.-1]*[min.sup.-1] iv) was measured with a Millar catheter. Collagen deposition, myocyte cross-sectional area, and expression of nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE), markers for ROS, were determined by histopathological and immunohistochemical staining. We found that the MI-induced increase in LV chamber dimension and the decrease in ejection fraction, an index of systolic function, were less severe in iNO[S.sup.-/-] compared with WT mice. l-NAME worsened LV remodeling and dysfunction further, and these detrimental effects were also attenuated in iNO[S.sup.-/-] mice, associated with better preservation of cardiac function. Lack of iNOS also reduced nitrotyrosine and 4-HNE expression after MI, indicating reduced oxidative stress. We conclude that iNOS does not seem to be a pathological mediator of heart failure; however, the lack of iNOS improves cardiac reserve post-MI, particularly when constitutive NOS isoforms are blocked. Decreased oxidative stress and other adaptive mechanisms independent of NOS may be partially responsible for such an effect, which needs to be studied further. oxidative stress; reactive oxygen species; ejection time
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- 2005
26. N-acetyl-seryl-aspartyl-lysyl-proline stimulates angiogenesis in vitro and in vivo
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Wang, Dahai, Carretero, Oscar A., Yang, Xiao-Yi, Rhaleb, Nour-Eddine, Liu, Yun-He, Liao, Tang-Dong, and Yang, Xiao-Ping
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Cells -- Research ,Heart attack -- Research ,Biological sciences - Abstract
N-acetyl-seryl-aspartyl-lysyl-proline stimulates angiogenesis in vitro and in vivo. Am J Physiol Heart Circ Physiol 287: H2099-H2105, 2004. First published July 15, 2004; doi: 10.1152/ajpheart.00592. 2004.--N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a natural inhibitor of pluripotent hematopoietic stem cell proliferation, has been suggested as capable of promoting an angiogenic response. We studied whether Ac-SDKP stimulates endothelial cell proliferation, migration, and tube formation; enhances angiogenic response in the rat cornea after implantation of a tumor spheroid; and increases capillary density in rat hearts with myocardial infarction (MI). In vitro, an immortal BALB/c mouse aortic endothelial 22106 cell line was used to determine the effects of Ac-SDKP on endothelial cell proliferation and migration and tube formation. In vivo, a 9L-gliosarcoma cell spheroid (250-300 [micro]m in diameter) was implanted in the rat cornea and vehicle or Ac-SDKP (800 [micro]g * [kg.sup.-1] * [day.sup.-1] ip) infused via osmotic minipump. Myocardial capillary density was studied in rats with MI given either vehicle or Ac-SDKP. We found that Ac-SDKP 1) stimulated endothelial cell proliferation and migration and tube formation in a dose-dependent manner, 2) enhanced corneal neovascularization, and 3) increased myocardial capillary density. Endothelial cell proliferation and angiogenesis stimulated by Ac-SDKP could be beneficial in cardiovascular diseases such as hypertension and MI. Furthermore, because Ac-SDKP is mainly cleaved by ACE, it may partially mediate the cardioprotective effect of ACE inhibitors. endothelial cell; capillaries; myocardial infarction
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- 2004
27. Left ventricular targeting of reporter gene expression in vivo by human BNP promoter in an adenoviral vector
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LaPointe, Margot C., Yang, Xiao-Ping, Carretero, Oscar A., and He, Quan
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Genetic regulation ,Heart muscle -- Genetic aspects ,Gene expression -- Physiological aspects ,Cardiovascular agents -- Genetic aspects ,Cytomegaloviruses -- Genetic aspects ,Biological sciences - Abstract
To selectively introduce genes into the mouse myocardium, we used a recombinant adenovirus encoding a transgene composed of a cardiac-specific promoter [the proximal human brain natriuretic peptide (hBNP) promoter] coupled to a luciferase reporter gene (Ad.hBNPLuc). Activity in vitro and in vivo was compared with Ad.CMVLuc, which contained the cytomegalovirus (CMV) enhancer/promoter. We tested cell-specific and inducible regulation of Ad.hBNPLuc in vitro. Expression was higher in neonatal cardiac myocytes than in a fibroblast cell line and was induced by interleukin-1[beta], phenylephrine, and isoproterenol in myocytes. For in vivo experiments, Ad.hBNPLuc, Ad. CMVLuc, or vehicle was injected into the left ventricular (LV) free wall of the mouse heart. In Ad.hBNPLuc-injected mice, luciferase activity was only detected in the heart. In contrast, Ad.CMVLuc-injected mice had detectable luciferase activity in all tissues examined. Our studies indicate that 1) the cardiac-specific hBNP promoter and direct cardiac injection limit expression of the transgene to the LV free wall; and 2) transgene expression in vitro is inducible and cardiac myocyte specific. Thus the use of the proximal hBNP promoter in recombinant adenoviral vectors may allow cardiac-specific and inducible expression of therapeutic genes in vivo and prevent some of the side effects of systemic adenovirus administration. gene transfer; cardiac-specific promoter
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- 2002
28. Kinins and Cardiovascular Disease
- Author
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Carretero, Oscar A., primary, Yang, Xiao-Ping, additional, and Rhaleb, Nour-Eddine, additional
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- 2009
- Full Text
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29. Nystatin and valinomycin induce tubuloglomerular feedback
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Ren, Yilin, Yu, Hong, Wang, Hong, Carretero, Oscar A., and Garvin, Jeffrey L.
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Nystatin -- Physiological aspects ,Kidneys -- Physiological aspects ,Biological control systems -- Research ,Ionophores -- Physiological aspects ,Chloride channels -- Research ,Biological sciences - Abstract
Ren, Yilin, Hong Yu, Hong Wang, Oscar A. Carretero, and Jeffrey L. Garvin. Nystatin and valinomycin induce tubuloglomerular feedback. Am J Physiol Renal Physiol 281: F1102--F1108, 2001. First published September 21, 2001; 10.1152/ajprenal.00357.2001.--The macula densa expresses a luminal [Na.sup.+]-[K.sup.+]-2[Cl.sup.-] cotransporter and a basolateral [Cl.sup.-] conductance. Although it is known that cotransport of [Na.sup.+], [K.sup.+], and [Cl.sup.-] is the first step in tubuloglomerular feedback (TGF), subsequent steps are unclear. We hypothesized that [Na.sup.+]-[K.sup.+]-2[Cl.sup.-] entry via the luminal [Na.sup.+]-[K.sup.+]-2[Cl.sup.-] cotransporter elevates intracellular [Cl.sup.-], increases electrogenic Clefflux across the basolateral membrane, and depolarizes the macula densa, initiating TGF. We perfused afferent arterioles with macula densa attached. The macula densa was perfused with solutions containing either 5 mM [Na.sup.+] and 3 mM [Cl.sup.-] (low NaCl) or 80 mM [Na.sup.+] and 77 mM [Cl.sup.-] (high NaCl). When the macula densa perfusate was changed from low to high NaCl, afferent arteriole diameter decreased from 15.8 [+ or -] 0.8 to 13.1 [+ or -] 0.7 mm (P < 0.05). Adding 10 [micro] M furosemide to the macula densa lumen blocked TGF. When nystatin, a group I cation ionophore, was added to the macula densa lumen together with furosemide in the presence of low NaCl, it induced TGF (from 18.0 [+ or -] 1.5 to 15.6 [+ or -] 1.6 mm; P = 0.003). When valinomycin, a [K.sup.+]-selective ionophore, was added to the macula densa lumen together with furosemide in the presence of low NaCl containing 5 mM [K.sup.+], it did not induce TGF. Subsequent addition of 50 mM KCl to the macula densa perfusate induced TGF (from 21.7 [+ or -] 0.8 to 17.5 [+ or -] 1.3 mm; P = 0.0047; n = 6). Adding 50 mM KCl without valinomycin did not induce TGF. When 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB; 1 [micro] M), a [Cl.sup.-] channel blocker, was added to the bath, it blocked TGF induced by high NaCl, but did not block TGF induced by valinomycin plus 50 mM KCl. NPPB did not alter afferent arteriole constriction induced by norepinephrine. We concluded that increased NaCl in the lumen of the macula densa leads to influx of [Cl.sup.-] via the [Na.sup.+]-[K.sup.+]-2[Cl.sup.-] cotransporter. The accelerated transport increases intracellular [Cl.sup.-]. The subsequent exit of [Cl.sup.-] across the basolateral membrane via [Cl.sup.-] channels in turn leads to depolarization of the macula densa and thereby induces TGF. afferent arteriole; transport; chloride channel Received 1 December 2000; accepted in final form 16 July 2001
- Published
- 2001
30. Angiotensin II-induced dilated cardiomyopathy in Balb/c but not C57BL/6J mice
- Author
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Peng, Hongmei, Yang, Xiao-Ping, Carretero, Oscar A., Nakagawa, Pablo, DʼAmbrosio, Martin, Leung, Pablo, Xu, Jiang, Peterson, Edward L., González, Germán E., Harding, Pamela, and Rhaleb, Nour-Eddine
- Published
- 2011
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31. Mas receptor is translocated to the nucleus upon agonist stimulation in brainstem neurons from spontaneously hypertensive rats but not normotensive rats
- Author
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Cerniello, Flavia M, primary, Silva, Mauro G, additional, Carretero, Oscar A, additional, and Gironacci, Mariela M, additional
- Published
- 2019
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32. Contributors
- Author
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Asmar, Roland, primary, Basile, Jan N., additional, Beevers, D.G., additional, Beilin, Lawrence J., additional, Bilo, Grzegorz, additional, Black, Henry R., additional, Boerrigter, Guido, additional, Bone, Lee R., additional, Brunner, Hans, additional, Burnett, John C., additional, Calhoun, David A., additional, Campese, Vito M., additional, Carey, Robert M., additional, Caro, J. Jaime, additional, Carretero, Oscar A., additional, Chappell, Mark C., additional, Chrysant, George S., additional, Cutler, Jeffrey A., additional, Dahlöf, Björn, additional, da Silva, Alexandre A., additional, de Faire, Ulf, additional, Delgado, Maria Carolina, additional, Devereux, Richard B., additional, Diamond, Joseph A., additional, DiPette, Donald J., additional, Diz, Debra I., additional, Edelman, Jonathan M., additional, Elliott, William J., additional, Ekman, Steffan, additional, Falkner, Bonita, additional, Fan, William L., additional, Fenichel, Robert R., additional, Ferrario, Carlos M., additional, Franklin, Stanley S., additional, Freis, Edward D., additional, Frishman, William H., additional, Frohlich, Edward D., additional, Funder, John W., additional, Fyhrquist, Frej, additional, Gamba, Gerardo, additional, Gami, Apoor S., additional, Gavras, Haralambos, additional, Gavras, Irene, additional, Gehr, Todd W.B., additional, Gleim, Gilbert W., additional, Hall, John E., additional, Hanes, Donna S., additional, Harrap, tephen B., additional, Harris, Katherine E., additional, Haus, Erhard, additional, Hermida, Ramon C., additional, Hill, Martha N., additional, Ibsen, Hans, additional, Intengan, Hope, additional, Izzo, Joseph L., additional, Jennings, Garry L.R., additional, Johnson, Ernest F., additional, Johnston, Colin I., additional, Jones, Daniel W., additional, Julius, Stevo, additional, Kannel, William B., additional, Katki, Khurshed A., additional, Kjeldsen, Sverre E., additional, Kleyman, Thomas R., additional, Knepper, Mark A., additional, Kokkoris, Panagiotis, additional, Kostis, John B., additional, Krakoff, Lawrence R., additional, Kristianson, Krister J., additional, Kuo, Jay J., additional, Lakkis, Jay, additional, Laragh, John H., additional, Levine, David M., additional, Light, Kathleen C., additional, Lindholm, Lars H., additional, Liu, Jiankang, additional, Lüscher, Thomas F., additional, Mancia, Giuseppe, additional, Mansoor, George A., additional, McCarron, David A., additional, McGuire, Heather L., additional, McInnes, Gordon T., additional, McMahon, Ellen G., additional, Meyer, Renee P., additional, Miller, Nancy Houston, additional, Nadim, Mitra K., additional, Nesbitt, Shawna D., additional, Neutel, Joel M., additional, Nieminen, Markku S., additional, Nussberger, Jürg, additional, Omvik, Per, additional, Oparil, Suzanne, additional, Opie, Lionel H., additional, Osterberg, Lars, additional, Parati, Gianfranco, additional, Payne, Krista A., additional, Pedersen, Ole Lederballe, additional, Phillips, Robert A., additional, Pi-Sunyer, Xavier, additional, Plat, Francis, additional, Pool, James L., additional, Portaluppi, Francesco, additional, Prisant, L. Michael, additional, Puddey, Ian B., additional, Raj, Satish R., additional, Reaven, Gerald M., additional, Reeves, Scott T., additional, Reinberg, Alain, additional, Reiser, Ira W., additional, Reudelhuber, Timothy L., additional, Reusser, Molly E., additional, Reves, J.G., additional, Rhaleb, Nour-Eddine, additional, Robertson, David, additional, Roccella, Edward J., additional, Rudd, Peter, additional, Ruddy, Michael C., additional, Ruilope, Luis Miguel, additional, Schiffrin, Ernesto L., additional, Schirger, John A., additional, Schork, M. Anthony, additional, Shepherd, Alexander M.M., additional, Sica, Domenic A., additional, Siragy, Helmy M., additional, Smith, Beverly A., additional, Smolensky, Michael H., additional, Snapinn, Steven, additional, Somers, Virend K., additional, Spieker, Lukas E., additional, Spitalewitz, Samuel, additional, Stolt, Pelle, additional, Supowit, Scott C., additional, Svetkey, Laura P., additional, Taler, Sandra J., additional, Tallam, Lakshmi S., additional, Tallant, E. Ann, additional, Tikellis, Chris, additional, Turnbull, Fiona, additional, Vidt, Donald G., additional, Watson, Ralph E., additional, Weber, Michael A., additional, Wedel, Hans, additional, Weder, Alan B., additional, Weinberger, Myron H., additional, Weir, Matthew R., additional, White, William B., additional, Wofford, Marion R., additional, Wong, Nathan D., additional, Wright, Jackson T., additional, Yang, Xiao-Ping, additional, Young, William F., additional, Zanchetti, Alberto, additional, and Zhao, Huawei, additional
- Published
- 2005
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33. The Kallikrein-Kinin System as a Regulator of Cardiovascular and Renal Function
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Carretero, Oscar A., primary, Yang, Xiao-Ping, additional, and Rhaleb, Nour-Eddine, additional
- Published
- 2005
- Full Text
- View/download PDF
34. The kinin B1 receptor contributes to the cardioprotective effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in mice
- Author
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Xu, Jiang, Carretero, Oscar A., Shesely, Edward G., Rhaleb, Nour-Eddine, Yang, James J., Bader, Michael, and Yang, Xiao-Ping
- Published
- 2009
- Full Text
- View/download PDF
35. Inhibition of p38 mitogen-activated protein kinase protects the heart against cardiac remodeling in mice with heart failure resulting from myocardial infarction
- Author
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Liu, Yun-He, Wang, Dahai, Rhaleb, Nour-Eddine, Yang, Xiao-Ping, Xu, Jiang, Sankey, Steadman S., Rudolph, Amy E., and Carretero, Oscar A.
- Published
- 2005
- Full Text
- View/download PDF
36. Sistema automático para el diseño preliminar de pilas de combustible de metanol directo
- Author
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Santiago Carretero, Oscar, Aranda Rosales, María, Navarro Arevalo, Emilio, Raso García, Miguel Ángel, and Leo Mena, Teresa de Jesus
- Subjects
Química - Abstract
Sistema automático para el diseño preliminar de pilas de combustible de metanol directo
- Published
- 2019
37. Hybridization of fuel cell-battery for small and light manned full electric aircrafts
- Author
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Sánchez Castañeda, Francisco Javier, Santiago Carretero, Oscar, Leo Mena, Teresa de Jesus, and Navarro Arévalo, Emilio
- Subjects
Energía Eléctrica ,Química - Abstract
Este estudio desarrolla una metodología para el dimensionamiento de un sistema de propulsión híbrido de pila de combustible-batería para aeronaves ligeras tripuladas que garantice la seguridad durante un vuelo en fase de crucero usando únicamente la pila de combustible. Para asegurar esta condición de vuelo seguro, se comprueba que la pila de combustible operando a su potencia nominal es capaz de mantener la velocidad de la aeronave por encima de los límites de seguridad en un vuelo con maniobras a altura constante. ----------ABSTRACT---------- This work develops a methodology for the sizing of a hybrid fuel cell-battery power system for small and light manned full electric aircrafts able to guarantee the security during the cruise flight stage only using the fuel cell. To assure this condition of a safe flight, it is tested that the fuel cell operating at its nominal power is able to maintain the velocity above security limits during a flight with maneuvers at a constant height.
- Published
- 2019
38. Sulfonated poly(vinyl alcohol)/graphene oxide composite membranes for proton exchange membrane fuel cells
- Author
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Ballester, S., Santiago Carretero, Oscar, Teruel Juanes, Roberto, Gil Castell, Oscar, Primaz, C., Pascual Jose, B., Badia, J.D., Leo Mena, Teresa de Jesus, Navarro Arévalo, Emilio, Soria, V., and Ribes Greus, A.
- Subjects
Energía Eléctrica ,Química - Abstract
Different crosslinked composite membranes of Poly(vinyl Alcohol) PVA with sulfosuccinic acid SSA as crosslinking agent and graphene oxide GO were prepared and characterized as a function of the sulfonating degree and GO percentage of each component. The chemical structure of membranes was confirmed by Fourier transform infrared spectroscopy FTIR. The good dispersion of GO into the polymer matrix was verified by scanning transmission microscopy SEM. The proton conductivity of the membranes in fully hydrated state was also investigated by electrochemical impedance spectroscopy EIS. To measure the potential use of PVA membranes as electrolyte were tested in a single proton exchange membrane fuel cell PEMFC. The results reveal that the addition of graphene oxide GO improves the thermal and mechanical stability of the composite membranes. The proton conductivity of the prepared membranes strongly increases by combination of matrix's sulfonating and introduction of GO nanoparticles. Thus, the sulfonating of the polymer matrix in the 30sPVA/SSA/GO membrane increases the proton conductivity a 42% and a 67% of maximum power density respect its homologue 30PVA/SSA membrane. In addition, 30sPVA/SSA/sGO membrane shows the lowest values of proton conductivity and maximum power density, which is consistent with the obtained water uptake values and confirms the improvement of barrier property of these composite membranes.
- Published
- 2019
39. Evaluation of recyclable polymeric materials for direct methanol fuel cell in marine and aeronautical applications
- Author
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Santiago Carretero, Oscar, Navarro Arévalo, Emilio, Carrillo Ramiro, Isabel, Meca Lopez, Vladimir Luis, Raso García, Miguel Ángel, Mora Peña, Eleuterio, and Leo Mena, Teresa de Jesus
- Subjects
Energía Eléctrica ,Ingeniería Naval - Abstract
Bipolar plates (BPs) of fuel cells represent about 80% of the mass, 30% of the cost and all volume of the stacks. Typically, graphite or metals such as stainless steel, aluminium or titanium are used as materials for BPs. However, graphite is not used at industrial level due to its brittleness. Metallic materials are more used, but they have high degradation rates and densities. In some applications, as portable devices or in aeronautical and naval vehicles, mass is a key factor. For these reasons, different composite materials are being studied for use as bipolar plates materials. In this work, seven thermoplastic materials are tested in order to analyse their behaviour as matrix for composite bipolar plates of direct methanol fuel cells (DMFC). Thermoplastic materials have been selected because of the possibility to be recyclable in such a way that the environmental impact is reduced. The materials tested are PLA (polylactic acid); ABS (acrylonitrile butadiene styrene); PC (polycarbonate); NY (nylon); TPU (thermoplastic polyurethane) and CPE and CPE+ (copolyester). Seven samples have been prepared with a 3D printer. These samples were immersed in a solution that simulates the conditions in a DMFC and its temperature is kept constant at 60 °C and a long-term experiment has been undertaken to study the degradation of the different samples with time. To assess the degradation features, 4 techniques have been used: mass loss, dimensional stability, hardness and absorbed moisture. By mass loss measurements it is concluded that the classification of the polymers according to their degradation rate is: PLA > NY > TPU > CPE = CPE+ > ABS = PC. Regarding the dimensional stability, the change of the thickness and planar surface of the samples has been analysed. The thickness of PLA, CPE and NY samples increases with time. NY samples also increase their planar surface. However, PLA and CPE reduce their planar surface so that a remarkable deformation occurs. By contrast, TPU samples reduce their thickness throughout the experiment, but keep their planar surface constant. ABS, PC and CPE+ are the most stable polymers since they keep constant both thickness and planar surface. In all cases, a slight decrease of hardness takes place with time. This reduction of hardness is more marked in NY, CPE+ and TPU, while the hardness of CPE samples is practically constant. The absorbed moisture percentage during the first 24 h shows that NY is the material with the higher moisture percentage (5.87%), while PC presents the lower values (0.19%) (NY > ABS > TPU >PLA > CPE+ > CPE > PC). In accordance with the results, the best materials for use as BPs in DMFCs are ABS and PC due to their reduced degradation rate and excellent dimensional stability.
- Published
- 2019
40. Effects of AT1 Receptor-Mediated Endocytosis of Extracellular Ang II on Activation of Nuclear Factor-κB in Proximal Tubule Cells
- Author
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ZHUO, JIA L., CARRETERO, OSCAR A., and LI, XIAO C.
- Published
- 2006
41. Cross-talk between angiotensin II and glucagon receptor signaling mediates phosphorylation of mitogen-activated protein kinases ERK 1/2 in rat glomerular mesangial cells
- Author
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Li, Xiao C., Carretero, Oscar A., and Zhuo, Jia L.
- Published
- 2006
- Full Text
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42. Chronic heart failure induced by coronary artery ligation in Lewis inbred rats
- Author
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Liu, Yun-He, Yang, Xiao-Ping, Nass, Omar, Sabbah, Hani N., Peterson, Edward, and Carretero, Oscar A.
- Subjects
Heart failure -- Physiological aspects ,Heart attack -- Models ,Rats as laboratory animals -- Physiological aspects ,Biological sciences - Abstract
The cardiac output, left ventricle pressure and central hemodynamics of Lewis inbred rats with or without heart failure (HF) were analyzed to determine the effects of HF on cardiac performance. Analysis of hemodynamics in rat models of chronic heart failure by left coronary artery ligation indicated the presence of left ventricle dysfunction due to large infarct size. The model of chronic heart failure in Lewis inbred rats exhibited low mortality and developed cardiac dysfunction and chamber dilation one week after myocardial infarction.
- Published
- 1997
43. Role of macula densa adenosine triphosphate (ATP) in tubuloglomerular feedback
- Author
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Ren, Yilin, Garvin, Jeffrey L., Liu, Ruisheng, and Carretero, Oscar A.
- Published
- 2004
- Full Text
- View/download PDF
44. Increased intracellular pH at the macula densa activates nNOS during tubuloglomerular feedback
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LIU, RUISHENG, CARRETERO, OSCAR A., REN, YILIN, and GARVIN, JEFFREY L.
- Published
- 2005
45. Vascular remodeling and the kallikrein-kinin system
- Author
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Carretero, Oscar A.
- Published
- 2005
46. Superoxide enhances tubuloglomerular feedback by constricting the afferent arteriole
- Author
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Liu, Ruisheng, Ren, Yilin, Garvin, Jeffrey L., and Carretero, Oscar A.
- Published
- 2004
- Full Text
- View/download PDF
47. Role of angiotensin II type 2 receptors and kinins in the cardioprotective effect of angiotensin II type 1 receptor antagonists in rats with heart failure
- Author
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Liu, Yun-He, Yang, Xiao-Ping, Shesely, Edward G., Sankey, Steadman S., and Carretero, Oscar A.
- Published
- 2004
- Full Text
- View/download PDF
48. Dual inhibition of ACE and NEP provides greater cardioprotection in mice with heart failure
- Author
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Xu, Jiang, Carretero, Oscar A, Liu, Yun-He, Yang, Fang, Shesely, Edward G, Oja-Tebbe, Nancy, and Yang, Xiao-Ping
- Published
- 2004
- Full Text
- View/download PDF
49. Role of a selective aldosterone blocker in mice with chronic heart failure
- Author
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Wang, Dahai, Liu, Yun-He, Yang, Xiao-Ping, Rhaleb, Nour-Eddine, Xu, Jiang, Peterson, Edward, Rudolph, Amy E, and Carretero, Oscar A
- Published
- 2004
- Full Text
- View/download PDF
50. Increased intracellular Ca++ in the macula densa regulates tubuloglomerular feedback
- Author
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REN, YILIN, LIU, RUISHENG, CARRETERO, OSCAR A., and GARVIN, JEFFREY L.
- Published
- 2003
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