Role of the renin-angiotensin system in blood pressure regulation. The cardiovascular effects of converting enzyme inhibition in normotensive subjects.

Abstract

SUMMARYThe role of the renin-angiotensin system in the regulation of blood pressure in normal human subjects was investigated by administering to them the converting enzyme inhibitor (SQ 20881) during sodium-replete and sodium-depleted states. In the sodium-replete state (150 m£q sodium intake for 5 days) in eight normal subjects, converting enzyme inhibitor decreased the average mean arterial pressure from 75 ± 4 to 65 ± 5 mm Hg (P < 0.005) because of a decrease in peripheral resistance from 17 ± 1 to 14 ± 1 U (P < 0.025). Cardiac output did not change because of a simultaneous decrease in venous return. Sodium depletion (10 mEq sodium intake for 5 days) in six subjects resulted in an insignificant decrease in blood pressure (from 7 5 ± 4 t o 6 9 ± 2 mm Hg), whereas cardiac output decreased from 5.15 ± 0.29 to 3.91 ± 0.22 liters/min (P < 0.05). Plasma renin activity increased with sodium depletion from 2.13 ± 0.38 to 7.3 ± 1.3 ng/ml per hour (P< 0.005). Converting enzyme inhibitor administration in the sodium-depleted state (n » 8) decreased mean arterial pressure from 69 ± 2 to 53 ± 5 mm Hg (P < 0.005) because of a decrease in peripheral resistance from 18 ± 1 to 12 ± 1 U (P < 0.005), whereas cardiac output increased from 3.91 ± 0.33 to 4.40 ± 0.30 liters/min (P < 0.005). The maximum decrease in diastolic blood pressure caused by the inhibitor correlated to the control plasma renin activity (r = 0.76, P < 0.01, n =• 14 measurements). These results indicate that the renin-angiotensin system participates in the regulation of blood pressure and cardiac function in normal subjects, even in the sodium-replete state. This role of the renin-angiotensin system in cardiovascular homeostasis in normal subjects becomes more crucial during sodium depletion when plasma renin (angiotensin II) is markedly increased. Cux Res 45:839-837, 1979 RECENT studies (Laragh, 1978) have provided evidence supporting a possible role for the reninangiotensin system in the pathogenesis and maintenance of elevated arterial pressure in essential and renovascular hypertension in human subjects. This pathogenetic role of angiotensin II has been investigated more precisely because of the availability, initially, of the angiotensin II competitive antagonist, saralasin (P 113), and, more recently, of the inhibitors of the angiotensin-converting enzyme. These agents, unlike saralasin, have no intrinsic agonistic activity, since they act by blocking the conversion of angiotensin I to angiotensin II, thereby eliminating the cardiovascular and endocrine effects of circulating angiotensin II. However, the participation of the renin-angiotensin system in the regulation of arterial pressure in normal human subjects has not been characterized fully because so far no complete hemodynamic measurements have been performed in normal subjects during converting enzyme inhibition. Haber and associates (Sancho et al., 1976;Haber, 1976), by administering the converting enzyme inhibitor in sodium-repleted and sodium-deprived normal subjects, concluded that angio...

A dose‐response study of HOE 498, a new non‐sulphydryl converting enzyme inhibitor, on blood pressure, pulse rate and the renin‐ angiotensin‐aldosterone system in normal man.

“…In the present study, blood pressure was lowered by active drug up to 24 h after dosing, the most consistent reduction being achieved after 2-3 h. The reduction of blood pressure after 5-50 mg of HOE 498 was comparable to that seen after enalapril and lisinopril in the dose range 5-20 mg, at 4-6 h after intake (Hodsman et al, 1984;MacGregor et al, 1981a;Millar et al, 1982) or 2 h after 25 mg of captopril (MacGregor et al, 1981b (Chinn & Dusterdieck, 1972;Atkinson & Robertson, 1979;Niarchos et al, 1979;MacGregor et al, 1981b). The effect of HOE 498 on plasma angiotensin II was seen to be more prolonged than that of captopril (MacGregor et al, 1581b) and of similar duration to that of enalapril (Brunner et al, 1981;MacGregor et al, 1981a;Hodsman et al, 1984) and lisinopril (Hodsman et al, 1984).…”

High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion

“…In addition to renal ACE, HF diet elevated Ang II in RIF of wild-type mice together with blood pressure and UACR, as was observed previously (5). The importance of RAS in the regulation of blood pressure and development of albuminuria is well recognized (20,26,(41)(42). Ang II is the principal RAS peptide regulating blood pressure and contributing to increased urinary albumin.…”

Pharmacodynamics of converting enzyme inhibition: the cardiovascular, endocrine and autonomic effects of MK421 (enalapril) and MK521.

“…There is also continuing debate on the relative contributions to the haemodynamic responses made by depressed levels of angiotensin II or increased levels of kinins, resulting from enzyme inhibition . This arises since both angiotensin I and bradykinin act as substrate for converting enzyme, otherwise known as kininase II. Absence of a reflex tachycardia during converting enzyme inhibition was noted with captopril (Fagard et al, 1981;Cody et al, 1979) and teprotide (Niarchos et al, 1979). The phenomenon suggests interruption of baroreceptor reflexes, and reduction of angiotensin Il-mediated facilitation of adrenergic neurotransmission has been documented in vitro (Collis & Keddie, 1981; Adigun et al, 1980).…”