Hypertension
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Primary aldosteronism is a severe form of autonomous aldosteronism. Milder forms of autonomous and renin-independent aldosteronism may be common, even in normotension. We characterized aldosterone secretion in 210 normotensives who had suppressed plasma renin activity (<1.0 ng/mL per hour), completed an oral sodium suppression test, received an infusion of angiotensin II, and had measurements of blood pressure and renal plasma flow. ⋯ Normotensives with evidence suggestive of confirmed primary aldosteronism had higher 24-hour urinary aldosterone excretion rate (20.2±12.2 versus 6.2±2.9 μg/24 hours; P<0.001) as expected, but also higher angiotensin II-stimulated aldosterone (12.4±8.6 versus 6.6±4.3 ng/dL; P<0.001) and lower 24-hour urinary sodium-to-potassium excretion (2.69±0.65 versus 3.69±1.50 mmol/mmol; P=0.001); however, there were no differences in age, aldosterone-to-renin ratio, blood pressure, or renal plasma flow between the 2 groups. These findings indicate a continuum of renin-independent aldosteronism and mineralocorticoid receptor activity in normotension that ranges from subtle to overtly dysregulated and autonomous. Longitudinal studies are needed to determine whether this spectrum of autonomous aldosterone secretion contributes to hypertension and cardiovascular disease.
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Acute kidney injury induced by ischemia/reperfusion (IR) is a frequent complication in hospitalized patients. Mineralocorticoid receptor antagonism has shown to be helpful against renal IR consequences; however, the potential benefit of novel nonsteroidal mineralocorticoid receptor antagonists such as finerenone has to be further explored. In this study, we evaluated the efficacy of finerenone to prevent the acute and chronic consequences of ischemic acute kidney injury. ⋯ After 4 months, the IR rats developed chronic kidney disease, evidenced by kidney dysfunction, increased proteinuria and renal vascular resistance, tubular dilation, extensive tubule-interstitial fibrosis, and an increase in kidney transforming growth factor-β and collagen-I mRNA. The transition from acute kidney injury to chronic kidney disease was fully prevented by finerenone. Altogether, our data show that in the rat, finerenone is able to prevent acute kidney injury induced by IR and the chronic and progressive deterioration of kidney function and structure.
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Age-related alterations in systemic and cerebral hemodynamics are not well understood. The purpose of this study is to characterize age-related alterations in beat-to-beat oscillations in arterial blood pressure (BP), heart rate (HR), cerebral blood flow (CBF), cardiac baroreflex sensitivity, and dynamic cerebral autoregulation across the adult life span. We studied 136 healthy adults aged 21 to 80 years (60% women). ⋯ Multiple linear regression analysis indicated that systolic BP variability is correlated positively with carotid-femoral pulse wave velocity independent of HR variability. In conclusion, advanced aging is associated with elevated pulsatility in BP and CBF; reduced beat-to-beat low-frequency oscillations in BP, HR, and CBF; and impaired baroreflex sensitivity and dynamic cerebral autoregulation at rest. The augmented BP and CBF variability in older adults during sit-stand maneuvers indicate diminished cardiovascular regulatory capability and increased hemodynamic stress on the cerebral circulation with aging.
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Preeclampsia is a severe complication of pregnancy. Antiangiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin are secreted in excess from the placenta, causing hypertension, endothelial dysfunction, and multiorgan injury. Oxidative stress and vascular inflammation exacerbate the endothelial injury. ⋯ PPIs upregulated endogenous antioxidant defenses and decreased cytokine secretion from placental tissue and endothelial cells. We have found that PPIs decrease sFlt-1 and soluble endoglin secretion and endothelial dysfunction, dilate blood vessels, decrease blood pressure, and have antioxidant and anti-inflammatory properties. They have therapeutic potential for preeclampsia and other diseases where endothelial dysfunction is involved.