Enhanced aldosterone response to angiotensin II in human hypertension.

Abstract

SUMMARY Adrenal and vascular responsiveness to graded doses of angiotensin II (A II) were recorded for seven normal subjects and 12 patients with essential hypertension while in balance on an intake of 200 mEq sodium/100 mEq potassium. Patients with essential hypertension had been previously studied and known to have normal responses of plasma renin activity to sodium restriction and upright posture. A l l was administered for 30 minutes at rates of 0.1, 0.3, 1, and 3 ng/kg per minute and plasma aldosterone responses were assessed 20 and 30 minutes later; blood pressure was monitored at intervals of 1 minute during infusion of A 11 at each rate. A significant increment in plasma aldosterone occurred at an infusion rate of 0.3 ng/kg per minute in patients with hypertension. This change was not seen until the infusion rate reached 1.0 ng/kg per minute in the normotensive control subjects. Even at an A II infusion rate of 1 ng/kg per minute, the increment in plasma aldosterone levels in normotensive subjects (4.2 ± 0.6 ng/dl) was significantly less (P < 0.001) than that in patients with essential hypertension (19 ± 3 ng/dl). In both groups, a significant rise in mean arterial blood pressure occurred at an A II dose of 0.3 ng/kg per minute, but the pressor response of the hypertensive group was significantly greater at the highest infusion rate (3 ng/kg per minute) (P < 0.05). Thus, enhanced adrenal and pressor responsiveness to infused A II was observed in the hypertensive subjects, suggesting a change in A II receptor affinity.ANGIOTENSIN II may play an important role in the control of blood pressure through its vasoconstrictor activity as well as its effects on volume homeostasis exerted through regulation of aldosterone secretion. However, previous studies evaluating adrenal and vascular responsiveness to infused angiotensin II (A II) in hypertensive subjects have yielded conflicting results.1 ' 6 Moreover, recent studies suggest that there may be physiologically important but functionally different receptors for A II on the adrenal cortex and vascular smooth muscle.7 ' 9 An imbalance of the relative responsivenes of these receptors to A II might lead to an imbalance in volume homeostasis or vasoconstrictor activity and thus produce an elevated blood pressure. The present study was designed to compare the relative magnitude of response of blood pressure and aldosterone secretion to graded doses of A II in patients with essential hypertension and normal subjects. MethodsTwelve patients with essential hypertension and seven normotensive control subjects were studied in the Clinical Research Center of the Peter Bent Brigham Hospital. The normotensive subjects (five male, two female) ranged in age from 23 to 38 years. They denied use of drugs and had no evidence of renal, cardiovascular, or endocrine abnormalities on routine screening. Patients with essential hypertension (eight male, four female) ranged in age from 24 to 68 years. The criteria for inclusion of patients with hyperten- sion in the study were as follo...

Role of the aldosterone system in the salt-sensitivity of patients with benign essential hypertension.

“…However, our findings suggest that this difference in aldosterone dynamics may be related to altered sensitivity of the adrenal cortex to changes in circulating angiotensin levels, because the ratio of the percentage changes of PA to those of PRA was significantly higher in the normotensive group than in the hypertensive group. This finding is compatible with the results of Kish et al,28) who demonstrated that responses of PA to infused angiotensin II were elevated in patients with essential hypertension who were on a diet containing 200mEq of sodium and 100mEq of potassium per day. Also, Wisgerhof et al29) reported that the response of aldosterone secretion to infused angiotensin II was enhanced in patients with low-renin essential hypertension.…”

Angiotensin II, aldosterone and arterial pressure: a quantitative approach. Arthur C. Corcoran Memorial Lecture.

“…7 *~M Such subjects are of special interest in this context because they permit an evaluation of the effects of sodium depletion on the aldosterone response to angiotensin II in the absence of changes in the endogenous plasma angiotensin II concentration, and hence may reveal adrenocortical sensitizing mechanisms that are independent of the renin-angiotensin system. In a series of six anephric patients studied by Deheneffe et al, 84 sodium depletion led to highly significant enhancement of the response of plasma aldosterone to infused angiotensin II, although this response remained distinctly below that of normal subjects.…”

Are Idiopathic Hyperaldosteronism and Low-Renin Hypertension Variants of Essential Hypertension?

“…An important point of distinction is that the response of aldosterone to infused angiotensin II is subnormal in Conn's syndrome (Mason et al, 1978;Brown et al, 1979). Thus in terms of their response, to angiotensin II, idiopathic hyperaldosteronism, low-renin hypertension, and essential hypertension are similar to each other but markedly different from Conn's syndrome (Table 2, see also Kisch et al, (1976), Brown and Wisgerhof (1978), Davies et al, (1979) andBrown et al (1979)). …”

“…The response of aldosterone to infused angiotensin II is also abnormally brisk (Kisch et al, 1976;Wisgerhof and Brown, 1978;Brown et al, 1979;Davies et al, 1979). Our own data show that for a given plasma concentration of angiotensin II, and for a given increment in plasma concentration, aldosterone increases more in essential hypertension than it does in normal subjects (Fig.…”