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BACKGROUND Obstructive sleep apnea (OSA) is associated with hypertension and the progression of chronic kidney disease (CKD). Renal sympathetic innervation contributes to either condition. METHODS We investigated the effect of renal sympathetic denervation (RDN) on blood pressure (BP), renal perfusion, and neurohumoral responses during and after repetitive obstructive apneas in a pig model for OSA. BP, femoral artery, and renal artery flow were measured in 29 spontaneously breathing urethane-chloralose–anesthetized pigs. The effect of RDN (n = 14) and irbesartan (n = 3) was investigated. Repetitive tracheal occlusions for 2 minutes with applied negative tracheal pressure at −80 mbar were performed over 4 hours. RESULTS Spontaneous breathing attempts during tracheal occlusion caused an intra-apneic breathing synchronous oscillating pattern of renal flow. Renal flow oscillations were >2-fold higher compared with femoral flow that almost showed changes proportional to the BP alterations (2.9%/mm Hg vs. 1.3%/mm Hg; P < 0.0001). A marked postapneic BP rise from 102±3 to 172±8 mm Hg (P < 0.00001) was associated with renal hypoperfusion (from 190±24 to 70±20ml/min; P < 0.00001) occurring after application of obstructive respiratory events. RDN, but not irbesartan, inhibited postapneic BP rises and renal hypoperfusion and attenuated increased plasma renin activity and aldosterone concentration induced by repetitive tracheal occlusions. Additionally, increased urinary protein/creatinine ratio was significantly reduced by RDN, whereas intra-apneic hemodynamic changes or blood gases were not modified by RDN. CONCLUSIONS Repetitive obstructive respiratory events result in postapneic BP rises and renal hypoperfusion, as well as neurohumoral responses and increased protein/creatinine ratio. These changes are mainly sympathetically driven because they could be attenuated by RDN. [ABSTRACT FROM AUTHOR]

BACKGROUND Glomerular hyperfiltration may contribute to the high incidence of renal disease in Obese African Americans essential hypertensive (ObAAEH) patients, but the precise mechanisms responsible for renal injury have not been elucidated. Mitochondria are important determinants of renal injury in hypertension, and increased levels of mitochondrial DNA (mtDNA) in the urine may indicate renal mitochondrial injury. We hypothesized that urine mtDNA copy numbers would be higher in ObAAEH compared to Caucasian essential hypertensive (CEH) patients. METHODS We prospectively measured systemic, renal vein (RV), inferior vena cava (IVC), and urinary copy number of the mtDNA genes COX3 and ND1 by quantitative-PCR in CEH and ObAAEH patients during constant sodium intake and antihypertensive regimens, and compared them with healthy volunteers (HV) (n = 23 each). RESULTS Blood pressure was similarly elevated in CEH and ObAAEH, while glomerular filtration rate (GFR) was higher and age lower in ObAAEH. Urinary (but not plasma) COX3 and ND1 were higher in CEH compared to HV, and further elevated in ObAAEH patients. COX3 and ND1 renal gradients (RV-IVC) were higher in ObAAEH vs. CEH, and their urinary levels directly correlated with GFR. In multivariate analysis, GFR remained the only predictor of elevated urinary COX3 and ND1 levels. CONCLUSIONS Urinary fragments of the mitochondrial genome are elevated in ObAAEH patients and correlate with glomerular hyperfiltration. A positive gradient across the kidney in ObAAEH suggests selective renal release. These results are consistent with mitochondrial injury that may aggravate renal damage and accelerate hypertension-related morbidity/ mortality rates in ObAAEH. [ABSTRACT FROM AUTHOR]

BACKGROUND Excessive maternal immune system activation plays a central role in the development of the hypertensive disorder of pregnancy preeclampsia (PE). The immunomodulatory cytokines interleukin 4 (IL-4) and interleukin 10 (IL-10) are dysregulated during PE; therefore we hypothesized that treatment with both recombinant IL-4 and IL-10 during pregnancy could prevent the development of PE in mice. METHODS Using our mouse model of PE in which immune system activation is induced by the double-stranded RNA receptor agonist poly I:C, we gave daily injections of IL-4, IL-10, or both on days 13–17 of pregnancy. Mice were then killed on day 18. RESULTS Poly I:C caused a significant increase in systolic blood pressure in pregnant (P-PIC) mice compared with vehicle-treated pregnant (P) mice. All 3 treatments significantly decreased blood pressure in P-PIC mice to P levels, ameliorated the endothelial dysfunction, and decreased placental TLR3 levels in P-PIC mice. However, only IL-4/IL-10 cotreatment prevented the proteinuria and increased incidence of fetal demise in P-PIC mice; IL-4 or IL-10 alone had no effect. Additionally, only IL-4/IL-10 cotreatment prevented the significant increase in CD3+/γδ+ T cells and CD11c+ dendritic cells and significant decrease in CD11b+/CD14− suppressor monocytes, as well as completely prevented placental necrosis, in P-PIC mice. Importantly, IL-4/IL-10 cotreatment in P mice had no detrimental effects. CONCLUSIONS Taken together, these data demonstrate that exogenous IL-4 and IL-10 administration concurrently during pregnancy can normalize immune cell subsets and prevent PE induced by maternal immune system activation. [ABSTRACT FROM PUBLISHER]

BACKGROUND Preeclampsia is a major cause of maternal and neonatal mortality and morbidity. The incidence of preeclampsia seems to be rising because of increased prevalence of predisposing disorders, such as essential hypertension, diabetes, and obesity, and there is increasing evidence to suggest widespread microcirculatory abnormalities before the onset of preeclampsia. We hypothesized that quantifying capillary rarefaction could be helpful in the clinical prediction of preeclampsia. METHODS We measured skin capillary density according to a well-validated protocol at 5 consecutive predetermined visits in 322 consecutive white women, of whom 16 subjects developed preeclampsia. RESULTS We found that structural capillary rarefaction at 20–24 weeks of gestation yielded a sensitivity of 0.87 with a specificity of 0.50 at the cutoff of 2 capillaries/field with the area under the curve of the receiver operating characteristic value of 0.70, whereas capillary rarefaction at 27–32 weeks of gestation yielded a sensitivity of 0.75 and a higher specificity of 0.77 at the cutoff of 8 capillaries/field with area under the curve of the receiver operating characteristic value of 0.82. Combining capillary rarefaction with uterine artery Doppler pulsatility index increased the sensitivity and specificity of the prediction. Multivariable analysis shows that the odds of preeclampsia are increased in women with previous history of preeclampsia or chronic hypertension and in those with increased uterine artery Doppler pulsatility index, but the most powerful and independent predictor of preeclampsia was capillary rarefaction at 27–32 weeks. CONCLUSIONS Quantifying structural rarefaction of skin capillaries in pregnancy is a potentially useful clinical marker for the prediction of preeclampsia. [ABSTRACT FROM PUBLISHER]

BackgroundCapillary rarefaction is pathognomonic of essential hypertension. We have previously shown significant capillary rarefaction in normotensive adult offspring of hypertensive parents, suggesting a familial predisposition in which capillary rarefaction represents a primary vascular abnormality that antedates the onset of sustained elevation of blood pressure (BP). We have recently reported that low-birth weight (LBW) infants, born at term or preterm, to normotensive mothers do not have capillary rarefaction at birth. We hypothesized that infants born to mothers with hypertensive disorders of pregnancy (HDP) would have significant capillary rarefaction at birth when compared to infants of normotensive mothers.MethodsWe studied 22 infants born to hypertensive mothers and compared them to 40 normal birth weight infants born at term to normotensive mothers. We used orthogonal polarized spectroscopy to measure basal (i.e., functional) and maximal (i.e., structural) skin capillary densities according to a well-validated protocol.ResultsWe found that term infants born to hypertensive mothers had significantly lower maximal capillary density (MCD) (mean difference of −5.0 capillaries/mm2; P < 0.05). However, preterm infants with LBW born to hypertensive mothers tended to have higher basal and maximal skin capillary densities compared with term infants.ConclusionsWhile the results in term infants are consistent with our belief that capillary rarefaction in essential hypertension is likely to be a primary vascular abnormality, the results in preterm infants may suggest that the intrauterine environment may exert some influences on the remodeling of the microcirculation which may delay the onset of capillary rarefaction in these infants.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.51 [ABSTRACT FROM AUTHOR]

BackgroundWe recently reported that aldosterone-induced cellular senescence via an increase in p21, a cyclin-dependent kinase (CDK) inhibitor, in rat kidney and cultured human proximal tubular cells. In the present study, we investigated the contribution of aldosterone to the renal p21 expression and senescence during the development of angiotensin II (AngII)-induced hypertension.MethodsMice received 1% salt in drinking water and vehicle or AngII, and were divided into five groups: 1, vehicle; 2, AngII; 3, AngII+olmesartan; 4, AngII+eplerenone; and 5, AngII+hydralazine.ResultsPlasma aldosterone levels were increased by AngII infusion. Eplerenone further elevated the plasma aldosterone level, but olmesartan and hydralazine did not. AngII group showed significant increase in blood pressure compared to vehicle. Olmesartan and hydralazine, but not eplerenone, suppressed the AngII-salt hypertension. The increase in urinary protein excretion by AngII-salt was suppressed only by olmesartan. AngII with high salt induced a greater expression of p21 mRNA in the kidney than vehicle. Olmesartan abolished the increase in p21 expression, whereas neither eplerenone nor hydralazine affected it. AngII with high salt did not change the expression of p16, another CDK inhibitor. The mice lacking p21 showed identical changes on blood pressure and albuminuria in response to AngII with high salt compared to wild type.ConclusionThese results suggest that aldosterone does not predominantly contribute to renal p21 expression and senescence during the development of AngII-salt hypertension, and that the increase in p21 in the kidney is not likely involved in the development of hypertension and albuminuria.American Journal of Hypertension (2012); doi:10.1038/ajh.2011.224 [ABSTRACT FROM AUTHOR]

BackgroundProgression of atherosclerosis with increased arterial stiffness is associated with increased cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Compliance index (CI) derived from digital volume pulse (DVP), measuring the relationship between volume and pressure changes in fingertip, can evaluate the local arterial stiffness. The purpose of this study was to measure the stiffness of different arteries and determine the relationships of CI-DVP with clinical characteristics and renal function in CKD patients.MethodsThis cross-sectional pilot study included 186 CKD and 46 healthy subjects. Evaluation of different arterial stiffness was performed by DVP using dual-channel photoplethysmography and measured as CI (CI-DVP) and pulse wave velocity (PWV)-DVP.ResultsCKD patients had lower CI-DVP and higher PWV-DVP than that in the healthy group. There was a trend of stepwise decrease in CI-DVP and increase in PWV-DVP related to the advance of CKD from early to late stage. Decrease of CI-DVP was associated with the increase in number of cardiovascular risk factors. Multivariate linear regression analysis revealed that CI-DVP (B = 4.59, P < 0.01) was independently associated with estimated glomerular filtration rate (eGFR). Male gender, eGFR, and systolic blood pressure (BP) were independent determinants for CI-DVP (B = −0.25, P = 0.01; B = 0.007, P = 0.03; and B = −0.03, P < 0.0001; whole model R2 = 0.28, P < 0.0001).ConclusionsOur data demonstrate a significant association between CI-DVP, a new surrogate marker of arterial stiffness different from PWV, and renal function and cardiovascular risk factors in CKD patients.American Journal of Hypertension (2011). doi:10.1038/ajh.2010.266 [ABSTRACT FROM AUTHOR]

BackgroundPreeclampsia (PE), a pregnancy-specific hypertensive syndrome, is one of the leading causes of premature births as well as fetal and maternal death. There is strong evidence that maternal immune system activation, of which Toll-like receptors (TLRs) play a major role, contributes to the development of PE. Viral infections, sensed by TLR3, are associated with hypertensive disorders of pregnancy. We tested the hypothesis that TLR3 activation during pregnancy would cause hypertension, endothelial dysfunction, proteinuria, and intrauterine growth restriction in normal pregnant rats.MethodsWe treated pregnant and nonpregnant rats with the viral mimetic polyinosinic:polycytidylic acid (poly I:C) or vehicle every other day beginning at day 10 of gestation and measured systolic blood pressure, aortic vasodilation, urinary protein concentration, fetal growth, and serum and placental cytokine levels.ResultsPregnant rats treated with poly I:C displayed significantly elevated systolic blood pressures compared to pregnant rats and nonpregnant rats treated with poly I:C on day 18 of gestation. Poly I:C–treated pregnant rats also exhibited significantly decreased aortic vasodilation, significantly increased urinary protein concentrations, and had more malformed pups/litter. Additionally, poly I:C–treated rats exhibited a significant increase in placental TLR3 expression and proinflammatory/anti-inflammatory cytokine ratio compared to vehicle-treated rats. Poly I:C treatment of nonpregnant control rats had no effect on systolic blood pressure, aortic vasodilation, or urinary protein concentrations.ConclusionThese findings demonstrate that sustained maternal immune system activation via TLR3 during pregnancy causes PE-like symptoms in rats and suggest that viral infection during pregnancy may contribute to the development of PE.American Journal of Hypertension 2009; doi:10.1038/ajh.2009.185 [ABSTRACT FROM AUTHOR]

: BackgroundStudies in adults with chronic kidney diseases demonstrate that the orally available angiotensin II antagonist irbesartan reduces arterial pressure and pathological proteinuria, mostly with an excellent tolerability profile. Little information is available on irbesartan in childhood.: MethodsA total of 44 pediatric outpatients with chronic kidney disease (27 male and 17, aged 3.7 to 18 years, median 10 years) were given irbesartan once a day during 18 weeks for arterial hypertension (N = 23), proteinuria (N = 8), or both (N = 13).: ResultsIn patients with hypertension, the use of irbesartan 4.1 (3.1–5.3) mg/kg body weight daily (median and interquartile range) was associated with a decrease (P < .005) in arterial pressure by 17 (13–22)/10 (7–12) mm Hg. In patients with overt proteinuria the urinary protein excretion decreased (P < .01) during treatment with irbesartan (2.9 [2.0–4.8] mg/kg body weight) by 52 (0–75) mg/[m2 × h]), whereas plasma albumin increased (P < .05) by 4 (1–5) g/L. The frequency of abdominal pain, constipation, cough, diarrhea, dizziness, edema, fatigue, headache, insomnia, myalgia, orthostasis, and rash was similar before and with irbesartan. Plasma sodium slightly decreased, whereas plasma potassium increased, with irbesartan (P < .01).: ConclusionsIn pediatric patients with chronic kidney diseases, irbesartan given once a day for 18 weeks significantly reduces arterial pressure and proteinuria, with an excellent tolerability and side effect profile. [Copyright &y& Elsevier]

The article discusses a study about the role of renal nerves in hypertension. The study looks into the potential of the catheter-based renal nerve ablation (CBRNA) in reducing blood pressure in human patients with drug-resistant hypertension. It suggests that CBRNA lowered BP significantly and persistently in obese hypertensive dogs without a major change in renal function.

The article offers information regarding association between orthostatic symptoms and orthostatic hypotension (OH) which is a clinical condition defined by consensus as a fall in systolic and diastolic blood pressures (BPs). It mentions information on association between self-reported symptoms related to OH and the office determination of chronic kidney disease attributed to hypertension. It states that orthostatic BP dysregulation is associated to higher risk of silent cerebrovascular disease.