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Migration of monocytes-macrophages plays an important role in phagocytosis of pathogens and cellular debris in a variety of pathophysiological conditions. Although epithelial Na+ channels (ENaCs) are required for normal migratory responses in other cell types, their role in macrophage migration signaling is unknown. To address this possibility, we determined whether ENaC message is present in several peripheral blood monocyte cell populations and tissue-resident macrophages in healthy humans using the Human Protein Atlas database (www.proteinatlas.org) and the mouse monocyte cell line RAW 264.7 using RT-PCR. We then determined that selective ENaC inhibition with amiloride inhibited chemotactic migration (50%), but not phagocytosis, of the mouse monocyte-macrophage cell line RAW 264.7. Furthermore, we generated a cell line stably expressing an NH2-terminal truncated aENaC to interrupt normal channel trafficking and found it suppressed migration. Prolonged exposure (48 h) of RAW 264.7 cells to proinflammatory cytokines interferon c (IFNγ) and/or tumor necrosis factor a (TNFa) inhibited RAW 264.7 migration and abolished the amiloride (1 mM)-sensitive component of migration, a finding consistent with ENaC downregulation. To determine if proinflammatory cytokines regulate aENaC protein expression, cells were exposed to proinflammatory cytokines IFNc (10 ng/mL, last 48 h) and TNFa (10 ng/mL, last 24 h). By Western blot analysis, we found whole cell aENaC protein is reduced 50%. Immunofluorescence demonstrated heterogeneous aENaC inhibition. Finally, we found that overnight exposure to amiloride stimulated morphological changes and increased polarization marker expression. Our findings suggest that ENaC may be a critical molecule in macrophage migration and polarization. [ABSTRACT FROM AUTHOR]

The pregnant Dahl salt-sensitive (S) rat is an established preclinical model of superimposed spontaneous preeclampsia characterized by exacerbated hypertension, increased urinary protein excretion, and increased fetal demise. Because of the underlying immune system dysfunction present in preeclamptic pregnancies in humans, we hypothesized that the pregnant Dahl S rat would also have an altered immune status. Immune system activation was assessed during late pregnancy in the Dahl S model and compared with healthy pregnant Sprague-Dawley (SD) rats subjected to either a sham procedure or a procedure to reduce uterine perfusion pressure (RUPP). Circulating immunoglobulin and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA) and Milliplex bead assay, respectively, and percentages of circulating, splenic, and placental immune cells were determined using flow cytometry. The pregnant Dahl S rat exhibited an increase in CD4þ T cells, and specifically TNFaþCD4þ T cells, in the spleen compared with virgin Dahl S rats. The Dahl also had increased neutrophils and decreased B cells in the peripheral blood as compared with Dahl virgin rats. SD rats that received the RUPP procedure had increases in circulating monocytes and increased IFN-ɣþCD4þ splenic T cells. Together these findings suggest that dysregulated T cell activity is an important factor in both the pregnant Dahl S rats and SD rats after the RUPP procedure. [ABSTRACT FROM AUTHOR]

Preeclampsia is characterized by increases in blood pressure and proteinuria in late pregnancy, and neurological symptoms can appear in the form of headaches, blurred vision, cerebral edema, and, in the most severe cases, seizures (eclampsia). The causes for these cerebral manifestations remain unknown, so the use of animal models that mimic preeclampsia is essential to understanding its pathogenesis. The Dahl salt-sensitive (Dahl SS/jr) rat model develops spontaneous preeclampsia superimposed on chronic hypertension; therefore, we hypothesized that the Dahl SS/jr rat would display cerebrovascular features similar to those seen in human preeclampsia. Furthermore, we predicted that this model would allow for the identification of mechanisms underlying these changes. The pregnant Dahl SS/jr rat displayed increased cerebral edema and blood-brain barrier disruption despite tighter control of cerebral blood flow autoregulation and vascular smooth muscle myogenic tone. Analysis of cerebral endothelial cell morphology revealed increased opening of tight junctions, basement membrane dissolution, and vesicle formation. RNAseq analysis identified that genes related to endothelial cell tight junctions and blood-brain barrier integrity were differentially expressed in cerebral vessels from pregnant Dahl SS/jr compared with healthy pregnant Sprague Dawley rats. Overall, our data reveal new insights into mechanisms involved in the cerebrovascular dysfunction of preeclampsia. [ABSTRACT FROM AUTHOR]

Hypertension and kidney involvement are common in patients with autoimmune disease. Sodium intake is linked to hypertension in both human and animal studies. Evidence suggests that dietary salt may be an important environmental factor that promotes autoimmune activity. Therefore, we hypothesized that a long-term high-salt diet would accelerate the progression of autoimmunity, hypertension, and albuminuria during systemic lupus erythematosus (SLE), an autoimmune disease that predominantly affects young women and has a high prevalence of hypertension and renal disease. To test this hypothesis, an established experimental model of SLE (female NZBWF1 mice) that develops hypertension and renal disease was used. SLE mice were fed a high-salt (4% NaCl) or normal (0.4% NaCl) diet for 24 wk beginning at 10 wk of age and ending at 34 wk of age, a time by which female NZBWF1 mice typically have hypertension and exhibit signs of renal disease. Plasma anti-dsDNA autoantibodies were measured as an indicator of active SLE disease, and urinary albumin was monitored longitudinally as a marker of renal disease. Arterial pressure was measured in conscious, freely moving mice at 34 wk of age. Urinary endothelin-1 (ET-1) excretion, renal endothelin A and B receptor protein expression, and renal mRNA expression of NOS1, NOS2, NOX2, MCP-1, TNF-α, serum- and glucocorticoid-regulated kinase 1, and interleukin-2 (IL-2) were assessed to determine the impact on gene products commonly altered by a high-salt diet. SLE mice fed a high-salt diet had increased circulating autoantibodies, but the highsalt diet did not significantly affect albuminuria or arterial pressure. Urinary ET-1 excretion was increased, whereas renal endothelin A receptor and IL-2 expression were decreased in response to a high-salt diet. These data suggest that a chronic high-salt diet may not accelerate cardiovascular and renal consequences commonly associated with SLE. [ABSTRACT FROM AUTHOR]

Obesity is a risk factor for cardiovascular disease and is associated with increased plasma levels of the adipose-derived hormone leptin. Vascular smooth muscle cells (VSMC) express leptin receptors (LepR); however, their physiological role is unclear. We hypothesized that leptin, at levels to mimic morbid obesity, impairs vascular relaxation. To test this, we used control and VSM-LepR knockout mice (VSM-LepR KO) created with a tamoxifen-inducible specific Cre recombinase to delete the LepR gene in VSMC. Control (10-12 wk old) and VSM-LepR KO (10-12 wk old) mice were fed a diet containing tamoxifen (50 mg/kg) for 6 wk, after which vascular reactivity was studied in isolated carotid arteries using an organ chamber bath. Vessels were incubated with leptin (100 ng/ml) or vehicle (0.1 mM Tris·HCl) for 30 min. Leptin treatment resulted in significant impairment of vessel relaxation to the endothelial-specific agonist acetylcholine (ACh). When these experiments were repeated in the presence of the superoxide scavenger tempol, relaxation responses to ACh were restored. VSM-LepR deletion resulted in a significant attenuation of leptin-mediated impaired ACh-induced relaxation. These data show that leptin directly impairs vascular relaxation via a VSM-LepR-mediated mechanism, suggesting a potential pathogenic role for leptin to increase cardiovascular risk during obesity. [ABSTRACT FROM AUTHOR]

Cerebrovascular complications and increased risk of encephalopathies are characteristic of preeclampsia and contribute to 40% of preeclampsia/eclampsia-related deaths. Circulating tumor necrosis factor-α (TNF-α) is elevated in preeclamptic women, and infusion of TNF-α into pregnant rats mimics characteristics of preeclampsia. While this suggests that TNF-α has a mechanistic role to promote preeclampsia, the impact of TNF-α on the cerebral vasculature during pregnancy remains unclear. We tested the hypothesis that TNF-α contributes to cerebrovascular abnormalities during placental ischemia by first infusing TNF-α in pregnant rats (200 ng/day ip, from gestational day 14 to 19) at levels to mimic those reported in preeclamptic women. TNF-α increased mean arterial pressure (MAP, P < 0.05) and brain water content in the anterior cerebrum (P < 0.05); however, TNF-α infusion had no effect on blood-brain barrier (BBB) permeability in the anterior cerebrum or posterior cerebrum. We then assessed the role of endogenous TNF-α in mediating these abnormalities in a model of placental ischemia induced by reducing uterine perfusion pressure followed by treatment with the soluble TNF-α receptor (etanercept, 0.8 mg/kg sc) on gestational day 18. Etanercept reduced placental ischemia-mediated increases in MAP, anterior brain water content (P < 0.05), and BBB permeability (202 ± 44% in placental ischemic rats to 101 ± 28% of normal pregnant rats). Our results indicate that TNF-α mechanistically contributes to cerebral edema by increasing BBB permeability and is an underlying factor in the development of cerebrovascular abnormalities associated with preeclampsia complicated by placental ischemia. [ABSTRACT FROM AUTHOR]

De-spite preeclampsia being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for its pathogenesis have yet to be fully elucidated. Growing evidence indicates that reduced uteroplacental perfusion and the resulting placental ischemia triggers the cascade of events leading to this maternal disorder. While the well-established rat model of reduced uterine perfusion pressure (RUPP) is providing invaluable insight into the etiology of preeclampsia, the aim of this study was to develop a mouse model of reduced uterine perfusion to expand mechanistic investigation by incorporation with novel gene-targeted mice. To accomplish this aim, a sham surgical procedure or a restriction of blood flow at the abdominal aorta and the ovarian arteries was initiated at day 13 of gestation in C57BL/6J mice. Mean arterial pressure measured in conscious, chronically instrumented mice was significantly elevated in the RUPP (120 ± 4 mmHg) compared with the sham (104 ± 4 mmHg) mice at day 18 of gestation (P < 0.01). Placental ischemia reduced fetal weights (0.95 ± 0.04 and 0.80 ± 0.02 g; RUPP vs. Sham, respectively; P < 0.02) and increased circulating levels of antiangiogenic soluble fms-related tyrosine ki-nases (sFlt)-1 (P < 0.05) in the RUPP at day 18 of gestation. Plasma concentrations of sFlt-1 are increased in preeclamptic patients and in response to reduced uterine perfusion in the rat. Thus, these results suggest that the mouse model of reduced uterine perfusion is appli-cable to facilitate novel mechanistic investigation into the etiology of hypertension that results from placental ischemia during pregnancy. [ABSTRACT FROM AUTHOR]

Because of the preponderance of women affected by the chronic autoimmune disease systemic lupus erythematosus (SLE), estrogen is thought to contribute to SLE disease progression. This is supported by evidence from experimental animal models of SLE showing that removal of estrogen in young female mice delays autoantibody production and renal injury and lengthens survival. Blood pressure and changes in body composition are important cardiovascular risk factors that can be regulated by estrogens. Because cardiovascular disease is the leading cause of death in patients with SLE, we used an established female mouse model of SLE (NZBWF1) to test whether early life removal of estrogen impacts the development of hypertension and changes in body composition commonly associated with SLE. Eight-week-old female SLE and control mice (NZW/LacJ) underwent either a sham operation or ovariectomy. Body weight, body composition (fat and lean masses), and renal injury (albuminuria) were monitored until mice reached 34 wk of age, at which time mean arterial pressure was assessed in conscious animals by a carotid catheter. Early life removal of the ovaries delayed the onset of autoantibody production and albuminuria while causing an increase in body weight and fat mass. Blood pressure in the adult was not altered by early life removal of the ovaries. These data suggest that estrogens may have a permissive role for the development of SLE while helping to maintain normal body weight and composition, which is associated with reduced cardiovascular risk. [ABSTRACT FROM AUTHOR]

Preeclampsia is thought to arise from inadequate cytotrophoblast migration and invasion of the maternal spiral arteries, resulting in placental ischemia and hypertension. Evidence suggests that altered expression of epithelial Na+ channel (ENaC) proteins may be a contributing mechanism for impaired cytotrophoblast migration. ENaC activity is required for normal cytotrophoblast migration. Moreover, β-ENaC, the most robustly expressed placental ENaC message, is reduced in placentas from preeclamptic women. We recently demonstrated that heme oxygenase- 1 (HO-1) protects against hypertension in a rat model of placental ischemia; however, whether HO-1 regulation of β-ENaC contributes to the beneficial effects of HO-1 is unknown. The purpose of this study was to determine whether β-ENaC mediates cytotrophoblast migration and whether HO-1 enhances ENaC-mediated migration. We showed that placental ischemia, induced by reducing uterine perfusion suppressed, and HO-1 induction restored, β-ENaC expression in ischemic placentas. Using an in vitro model, we found that HO-1 induction, using cobalt protoporphyrin, stimulates cytotrophoblast β-ENaC expression by 1.5- and 1.8-fold (10 and 50 μM). We then showed that silencing of β-ENaC in cultured cytotrophoblasts (BeWo cells), by expression of dominant-negative constructs, reduced migration to 56 ± 13% (P < 0.05) of control. Importantly, HO-1 induction enhanced migration (43 ± 5% of control, P < 0.05), but the enhanced migratory response was entirely blocked by ENaC inhibition with amiloride (10 μM). Taken together, our results suggest that β-ENaC mediates cytotrophoblast migration and increasing β-ENaC expression by HO-1 induction enhances migration. HO-1 regulation of cytotrophoblast β-ENaC expression and migration may be a potential therapeutic target in preeclamptic patients. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder with prevalent hypertension and renal injury. In this study, we tested whether the renal nerves contribute to the development of hypertension in an established mouse model of SLE (NZBWF1). Female SLE and control (NZW/LacJ) mice were subjected to either bilateral renal denervation or a sham procedure at 32 wk of age. Two weeks later, blood pressure was assessed in conscious mice using carotid artery catheters. Blood pressure was higher in SLE mice compared with controls, as previously reported; however, blood pressure was not altered in the denervated SLE or control mice. The development of albuminuria was markedly blunted in denervated SLE mice; however, glomerulosclerosis was increased. Renal denervation reduced renal cortical expression of monocyte-chemoattractant protein in SLE mice but did not significantly alter renal monocyte/macrophage infiltration. Renal cortical TNF-α expression was also increased in sham SLE mice, but this was not impacted by denervation. This study suggests that the renal nerves do not have a significant role in the pathogenesis of hypertension, but have a complex effect on the associated renal inflammation and renal injury. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a risk factor for hypertension. Previously, we demonstrated that an established mouse model of SLE (female NZBWF1 mice) develops hypertension with renal inflammation and oxidative stress, both characteristics known as contributing mechanisms to the development of salt-sensitive hypertension. On the basis of this model, we hypothesized that blood pressure in SLE mice would be salt-sensitive. Thirty-week-old female SLE and control mice (NZW/LacJ) were fed 8% high-salt (HS) diet or normal diet (0.4% salt) for 4 wk. Plasma levels of double-stranded DNA (dsDNA) autoantibodies, a marker of SLE disease activity, were increased in SLE mice compared with controls (472 ± 148 vs. 57 ± 17 U/ml × 1,000, P < 0.001). HS did not alter dsDNA autoantibody levels in SLE or control mice. Mean arterial pressure was increased in SLE mice compared with controls (132 ± 3 vs. 118 ± 2 mmHg, P < 0.001) and was not significantly altered by the HS diet in either group. Similarly, albuminuria was higher in SLE mice compared with controls (10.7 ± 9.0 vs. 0.3 ± 0.1 mg/day) but was not significantly increased in SLE or control mice fed a HS diet. In summary, blood pressure during SLE is not salt-sensitive, and the HS diet did not adversely affect SLE disease activity or significantly augment albuminuria. These data suggest that renal inflammation and oxidative stress, characteristics common to both SLE and models of salt-sensitive hypertension, may have diverging mechanistic roles in the development of hypertension. [ABSTRACT FROM AUTHOR]

Inflammation and immune system dysfunction contributes to the development of cardiovascular and renal disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that carries a high risk for both renal and cardiovascular disease. While hemodynamic changes that may contribute to increased cardiovascular risk have been reported in humans and animal models of SLE, renal hemodynamics have not been widely studied. The renin-angiotensin system (RAS) plays a central role in renal hemodynamic control, and although RAS blockade is a common therapeutic strategy, the role of RAS in hemodynamic function during SLE is not clear. This study tested whether mean arterial pressure (MAP) and renal hemodynamic responses to acute infusions of ANG II in anesthetized animals were enhanced in an established female mouse model of SLE (NZBWF1). Baseline MAP was not different between anesthetized SLE and control (NZWLacJ) mice, while renal blood flow (RBF) was significantly lower in mice with SLE. SLE mice exhibited an enhanced pressor response and greater reduction in RBF after ANG II infusion. An acute infusion of the ANG II receptor blocker losartan increased RBF in control mice but not in mice with SLE. Renin and ANG II type 1 receptor expression was significantly lower, and ANG II type 2 receptor expression was increased in the renal cortex from SLE mice compared with controls. These data suggest that there are fewer ANG II receptors in the kidneys from mice with SLE but that the existing receptors exhibit an enhanced sensitivity to ANG II. [ABSTRACT FROM AUTHOR]

Blood pressure (BP) increases after menopause. However, the mechanisms responsible have not been elucidated. In this study we tested the hypothesis that 20-hydroxyeicosatetraenoic acids (20-HETE), produced by cytochrome P-450 (CYP450) ω-hydroxylase, contributes to the hypertension in a model of postmenopausal hypertension, aged female spontaneously hypertensive rats (PMR). 1-Aminobenzotriazole, a nonselective inhibitor of arachidonic acid metabolism, for 7 days, reduced BP in PMR but had no effect in young females. Acute intravenous infusion of HET-0016, a specific inhibitor of 20-HETE, over 3 h, also reduced BP in PMR. CYP4A isoform mRNA expression showed no difference in renal CYP4A1 or CYP4A3 but increases in CYP4A2 and decreases in CYP4A8. CYP4A protein expression was decreased in kidney of PMR compared with young females. Endogenous 20-HETE was significantly higher in cerebral vessels of PMR than young females (YF) but was significantly lower in renal vessels of PMR. Omega-hydroxylase activity in cerebral vessels was also higher in PMR but was similar in kidney vessels in both groups. In renal microsomal preparations, endogenous 20-HETE was not different in PMR and young females, but ?-hydroxylase activity was significantly lower in PMR than YF. The data with blockers suggest that 20-HETE contributes to postmenopausal hypertension in SHR. The data also suggest that cerebral production of 20-HETE may be increased and renal tubular production may be decreased in PMR, thus both contributing to their elevated BP. [ABSTRACT FROM AUTHOR]

Hindlimb suspension (HLS) elicits muscle atrophy, oxidative stress, and apoptosis in skeletal muscle. Increases in oxidative stress can have detrimental effects on muscle mass and function, and it can potentially lead to myonuclear apoptosis. Resveratrol is a naturally occurring polyphenol possessing both antioxidant and antiaging properties. To analyze the capacity of resveratrol to attenuate oxidative stress, apoptosis and muscle force loss were measured following 14 days of HLS. Young (6 mo) and old (34 mo) rats were administered either 12.5 mg·kg-1&#x00B7;day-1 of trans-resveratrol, or 0.1% carboxymethylcellulose for 21 days, including 14 days of HLS. HLS induced a significant decrease in plantarflexor isometric force, but resveratrol blunted this loss in old animals. Resveratrol increased gastrocnemius catalase activity, MnSOD activity, and MnSOD protein content following HLS. Resveratrol reduced hydrogen peroxide and lipid peroxidation levels in muscles from old animals after HLS. Caspase 9 abundance was reduced and Bcl-2 was increased, but other apoptotic markers were not affected by resveratrol in the gastrocnemius muscle after HLS. The data indicate that resveratrol has a protective effect against oxidative stress and muscle force loss in old HLS animals; however, resveratrol was unable to attenuate apoptosis following HLS. These results suggest that resveratrol has the potential to be an effective therapeutic agent to treat muscle functional decrements via improving the redox status associated with disuse. [ABSTRACT FROM AUTHOR]

Heme oxygenase (HO) is the enzyme responsible for the breakdown of heme-generating carbon monoxide (CO) and biliverdin in this process. HO-2 is the constitutively expressed isoform in most tissues, such as the kidney and vasculature. CO generated by HO is believed to be an important vasodilator in the renal circulation along with another gas, nitric oxide (NO). To determine the importance of HO-2 in the regulation of blood pressure and renal blood flow (RBF), we treated HO-2 knockout (KO) mice chronically with either ANG II or NG-nitroarginine methyl ester (L-NAME). Basal blood pressures were not different between wild- type (WT), heterozygous (HET), or KO mice and averaged 113 ± 3 vs. 115 ± 2 vs. 116 ± 2 mmHg. Similar increases in blood pressure to chronic ANG II as well as L-NAME treatment were observed in all groups with blood pressures increasing an average of 30 mmHg in response to ANG II and 15 mmHg in response to L-NAME. Basal RBFs were not different between the groups averaging 6.0 ± 0.5 (n  6) vs. 4.8 ± 0.6(n 10) vs. 5.8 ± 0.7 (n  6)ml∙min-1∙g-1 kidney weight in WT, HET, and KO mice. HO-2 KO and HET mice exhibited an attenuated decrease in RBF in response to acute administration of ANG II, while no differences were observed with L-NAME. Our data indicate that blood pressure and RBF responses to increased ANG II or inhibition of nitric oxide are not significantly enhanced in HO-2 KO mice. [ABSTRACT FROM AUTHOR]

Systemic lupus erytbematosus (SLE) is a chronic autoimmune inflammatory disorder that predominantly affects women during their reproductive years. Although SLE can affect any organ system, the kidneys are prominently involved in the form of immune complex glomerulonephritis. In addition, in women with SLE, risk for the development of cardiovascular disease is dramatically increased. Hypertension is a major risk factor for cardiovascular disease and is highly prevalent in women with SLE. Nevertheless, there has been little exploration of the pathophysiological mechanisms that promote SLE hypertension. This review discusses the role of several mechanisms, with an emphasis on the kidney, in SLE hypertension. These mechanisms include the renln-angiotansin system, endothelin, oxidative stress, sex steroids, metabolic changes, peroxisome proliferator-activated receptor-γ, and, perhaps most importantly, chronic inflammation and cytokines. Growing evidence suggests a link between chronic inflammation and hypertension. Therefore, elucidation of mechanisms that promote SLE hypertension may be of significant value not only for patients with SLE, but also for a better understanding of the basis for essential hypertension. [ABSTRACT FROM AUTHOR]

Women with systemic lupus erythematosus (SLE) exhibit a high prevalence of hypertension and renal injury. Rosiglitazone (Rosi), a peroxisome proliferator activator receptor gamma (PPARγ, agonist, has renal protective and antihypertansive effects. We tested whether Rosi ameliorates hypertension and renal injury in a female mouse model of SLE (NZBWFI). Thirty-week-old SLE and control (NZW/LacJ) mice (n ≥ 6/group) were fed Rosi (5 mg·kg-1day-1 in standard chow) or standard chow for 4 wk. SLE mice had increased blood pressure (BP in mmHg) compared with controls (139 ± 4 vs. 111 ± 4, P < 0.05). Rosi treatment lowered BP in SLE mice (127 ± 4, P < 0.05) but not in controls (Ill ± 4). Urinary albumin (μg/mg crantinine) was increased in SLE mice compared with controls (12,396 ± 6,525 vs. 50 ± 6) and reduced with Rosi treatment (148 ± 117). Glomerulosclerosis (% of glomcmli with sclerosis) was reduced in Rosi-treated SLE mice (4.2 ± 1.6 vs. 0.4 ± 0.3, P < 0.05). Renal monocyte/ macrophage numbers (cell number/I,320 points counted) were re- duced in SLE mice treated with Rosi (32.6 ± 11.0 vs. 10.6 ± 3.6, P < 0.05) but unchanged in controls (3.7 ± 1.6 vs. 3.7 ± 2.0). Renal osteopuntin expression, a cytokine-regulafing macrophage recruitment, was reduced in Rosi-treated SLE mice. Urinary endothelin (in pg/mg creatinine) was increased in SLE mice compared with controls (1.9 ± 0.59 vs. 0.6 ± 0.04, P < 0.05) and reduced in SLE mice treated with Rosi (0.8 ± 0.11, P < 0.05). PPARγ, protein expression in the renal cortex was significantly lower in SLE mice compared with controls and was unaffected by Rosi. These data suggest that Rosi may be an important therapeutic option for the treatment of SLE hypertension and renal injury. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that predominantly affects women during their reproductive years. Although women with SLE have hypertension, the underlying mechanisms for this have not been examined. Despite the fact that inflammation is associated with altered endothelial and vascular function, the role of altered vascular function in the development of hypertension during SLE is unclear. In the present study, we tested whether a mouse model of SLE (NZBWF1) develops hypertension and examined whether increased blood pressure was associated with impaired endothelial-dependent relaxation. Female NZBWF1 mice were studied at 8, 20, and 36 wk of age. By 36 wk, urinary albumin and antinuclear antibodies were increased in SLE compared with control mice. Mean arterial pressure, measured by radiotelemetry, was significantly increased in SLE mice (124 ± 4 mmHg, n = 10) compared with control NZW/LacJ mice (111 ± 3 mmHg, n = 7) at 36 wk. Isolated carotid arteries from NZBWF1 mice, precontracted with U-46619 for assessment of endothelial-dependent relaxation, demonstrated a progressively impaired relaxation to ACh with age, although endothelial nitric oxide synthase mRNA expression was not different. Maximal tension generated by 5-hydroxytryptamine was increased in carotid arteries from NZBWF1 mice compared with controls at 8, 20, and 36 wk of age, suggesting a role for altered vascular function early on in the progression of SLE. Taken together, our data support a role for altered endothelial function as a contributing factor to the development of hypertension during SLE. [ABSTRACT FROM AUTHOR]

The American Physiological Society officially recognized the area of research in Water and Electrolyte Homeostasis (WEH) over 30 years ago when the Section of WEH was established. This minireview illuminates the importance of WEH research to the physiology community. By the narrowest definition, WEH research studies the regulation of body fluids; however, this research area is much broader and more relevant today than when this subdiscipline was first recognized because of the translational and systemic "point of view" of WEH research. This minireview highlights how WEH research serves as a balanced force between the full range of other more traditional organ-based physiological and pathophysiological concepts. The breadth of research in which WEH investigators engage is on full display with the publication of minireviews from the annual Data Diuresis session at Experimental Biology. [ABSTRACT FROM AUTHOR]

The article discusses the study which examined the impact of peroxisome proliferator-activated receptor γ (PPARγ) to brown adipose tissue (BAT) of rats. PPARγ is a nuclear receptor and ligand-activated transcription factor while BAT is recognized for its functions in metabolic rate control of rodents. The study found that PPARγ agonist rosiglitazone enhances rat's BAT lipogenesis from glucose without altering glucose uptake.