The role of the renin-angiotensin-aldosterone system in cardiovascular homeostasis in normal human subjects.

Abstract

SUMMARY To examine the role of angiotensin II in the maintenance of blood pressure and the control of aldosterone secretion in man, eight normal subjects were studied on a tilt table in sodium replete and sodium depleted states prior to and subsequent to the intravenous infusion of an angiotensin converting enzyme inhibitor (CEI). In both the sodium replete or sodium depleted state, upright tilting resulted in an increase in heart rate and a narrowing of pulse pressure. None of the sodium replete or depleted subjects fainted. Tilting was accompanied by a rise in plasma renin activity with an associated rise in plasma aldosterone concentration. When converting enzyme inhibitor was administered, wbich blocked the generation of angiotensin II, sodium replete subjects were able to compensate for an upright tilt, despite the absence of angiotensin 11, without significant hemodynamic change when compared to control state. In sodium depleted subjects, after the administration of converting enzyme inhibitor, there was a sharp and significant decrease THE PRECISE ROLE of the renin-angiotensin system in the maintenance of blood pressure in normal human subjects remains unclear. The recent availability of effective competitive inhibitors of the angiotensin converting enzyme has permitted a critical examination of this question. Recent experiments in rats, rabbits, and trained conscious dogs' have demonstrated the importance of angiotensin II in the maintenance of blood pressure in the sodium depleted animal. In the experiments described here, the role of the renin-angiotensin system in the maintenance of blood pressure and in the regulation of aldosterone in relation to sodium depletion, diuretic administration, and posture was examined in normal human subjects. Methods Subjects Eight normal subjects (seven men, one woman), ranging in age from 19 to 27 years, were studied. All subjects were in in systolic and diastolic blood pressure associated with a significant rise in heart rate. All but one sodium depleted subject fainted within seven minutes. Both plasma aldosterone concentration and plasma renin activity rose on tilting in both sodium replete and sodium depleted subjects. After the administration of converting enzyme inhibitor, plasma aldosterone failed to rise in association with a rise in plasma renin activity. In supine subjects, after the administration of converting enzyme inhibitor, plasma renin activity rose but plasma aldosterone concentration fell. In sodium depleted subjects, after the administration of CEI, aldosterone fell to a level significantly lower than that in supine controls and to a level no different from the supine sodium replete subject. These results indicate that angiotensin II is essential for blood pressure maintenance in sodium depleted individuals, that angiotensin II exerts a direct feedback control on renin secretion, and that angiotensin It is the primary stimulus to aldosterone secretion in response to both sodium depletion and to posture.good health by history, had a normal physical ...

The effect of altered sodium balance upon renal vascular reactivity to angiotensin II and norepinephrine in the dog. Mechanism of variation in angiotensin responses.

“…However, in the experiments of Aiken and Vane, All and norepinephrinie were infused into the renal artery for 5-6 min, a duration of time adequate to induce prostaglandin synthesis in response to the vasoconstrictor actioni of the two hormones (21). On the other hand, in the present experiimient, All and( inorepinephriine were injected as bolus injectionis and the maximal reduction of renial blood flow (which almost always occurred withiin [5][6][7][8][9][10] In summary, the present studies demonstrate that the renal vascular reactivity to Al, was blunted by acute or chronic sodium depletion (which stimulates renin secretion) and was enhanced by acute sodium repletion or chronic administration of a high salt diet and DOCA (which suppress renin secretion) or by CEI (which presumably reduced the concentration of circulating All). The renal vascular reactivity to norepinephrine was not significantly influenced by alteration of sodium balance or by administration of converting enzyme (except for an enhancement of norepinephrine sensitivity which occurred after CEI in dogs pretreated with DOCA and salt).…”

“…During sodium depletion, there is an increase in the concentration of circulating angiotensin II (1). The administration to sodium-depleted animals or to huimans of pharmacological agents that prevent the formation of angiotensin 11 (All)' or that compete with this polypeptide for its vascular receptors, induces a drop in arterial blood pressure with little or no change in cardiac output (2)(3)(4)(5). Despite the fact that the vasoconstrictor action of Al appears to be essential for the maintenance of normal blood pressure during sodium depletion, the pressor and vascular responses to exogenously administered octapeptide are greatly reduced in this condition (6)(7)(8)(9)(10)(11)(12).…”

Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia.

“…These peptides have been assigned important roles in the regulation of blood pressure and transvascular fluid exchange by several investigators (4)(5)(6)(7)(8). Using a blood pressure response bioassay in intact, anesthetized dogs, we demonstrated that acute alveolar hypoxia impaired AI conversion (9).…”

Are centenarians genetically predisposed to lower disease risk?

“…The majority (~90%) of them lived most of their lives and were born in the same area of Spain (Meseta Castellana,~600 m altitude). (Zintzaras et al 2008;Sancho et al 1976), ischemic stroke (Slowik et al 2007) type II diabetes (Zhou et al 2009 Cardiorespiratory fitness in CAD (Defoor et al 2006;Wagoner et al 2002) 0 = GG, 1 = CG, 2 = CC ADRB2 Adrenergic, beta-2-, receptor…”