Hypertension
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Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. ⋯ In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes/Bacteroidetes ratio. These observations demonstrate that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension.
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Comparative Study
Effect of advanced maternal age on pregnancy outcomes and vascular function in the rat.
Advanced maternal age is becoming increasingly common in Western societies and is associated with increased maternal and fetal morbidity and mortality. We hypothesized that aging results in impaired vascular function in pregnancy because of increased vascular oxidative stress and resultant scavenging of nitric oxide in both uterine and systemic arteries, causing reduced uteroplacental perfusion and poor pregnancy outcomes. Using aged rats (9.5 months), we investigated the effect of a delayed first natural pregnancy on pregnancy outcomes and uterine and mesenteric artery function on gestational day 20. ⋯ However, mesenteric arteries from aged dams had a greater nitric oxide and a reduced endothelial-derived hyperpolarization contribution to methacholine-mediated vasodilation compared with young dams. Both uterine and mesenteric arteries from aged dams had greater active myogenic responses, with area under the curve increased by 228% and 151%, in aged uterine and mesenteric arteries, respectively. These results demonstrate that vascular function is altered at an advanced maternal age and provides further insights into the risks of poor pregnancy outcomes observed in women who delay pregnancy.
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Renal dopamine 2 receptor dysfunction is associated with oxidative stress and high blood pressure (BP). We have reported that DJ-1, an oxidative stress response protein, is positively regulated by dopamine 2 receptor in the kidney. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of several antioxidant genes. ⋯ An Nrf2 inducer, bardoxolone, normalizes the systolic BP and renal malondialdehyde levels in DJ-1(-/-) mice without affecting them in their wild-type littermates. Because Nrf2 ubiquitination is increased in DJ-1(-/-) mice, we conclude that the protective effect of DJ-1 on renal oxidative stress is mediated, in part, by preventing Nrf2 degradation. Moreover, renal dopamine 2 receptor and DJ-1 are necessary for normal Nrf2 activity to keep a normal redox balance and BP.
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Randomized Controlled Trial Multicenter Study
Magnitude of blood pressure reduction and clinical outcomes in acute intracerebral hemorrhage: intensive blood pressure reduction in acute cerebral hemorrhage trial study.
Evidence supports early intensive blood pressure (BP) lowering in acute intracerebral hemorrhage, but uncertainty persists over whether potential benefits and harms vary according to the magnitude of BP reduction. We aimed to determine whether larger systolic BP (SBP) reductions were associated with better outcomes in participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). INTERACT2 was an international, open, blinded end point, randomized controlled trial of patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated SBP (150-220 mm Hg) assigned to intensive (target SBP <140 mm Hg) or guideline-recommended (SBP <180 mm Hg) treatment. Associations of BP reduction (baseline minus average of achieved SBP) during 3 time periods post randomization (15-60 minutes, 1-24 hours, and 2-7 days) on poor outcome (death or major disability) at 90 days were analyzed in multivariable logistic regression models with odds ratios and 95% confidence intervals. Larger SBP reductions within the first hour after randomization were associated with lower risks of poor outcome: compared with minimal reduction (<10 mm Hg), odds ratios were 0.80 (95% confidence interval, 0.63-1.02) for moderate (10-20 mm Hg) and 0.65 (0.52-0.82) for large (≥20 mm Hg) reductions (P trend <0.01). Similar associations were also observed for SBP reductions during 1 to 24 hours (P<0.01) and 2 to 7 days (P 0.02). No heterogeneity in associations for patients above or below baseline SBP 180 mm Hg was reported (P>0.30). Optimal recovery from intracerebral hemorrhage was observed in hypertensive patients who achieved the greatest SBP reductions (≥20 mm Hg) in the first hour and maintained for 7 days. ⋯ URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.