Angiotensin II inhibition with captopril on plasma ADH, PG synthesis, and renal function in humans

Abstract

Using captopril (C), an angiotensin (ANG) I converting-enzyme inhibitor, to increase endogenous prostaglandins (PGs) and to decrease endogenous ANG II synthesis, we studied the relationship between endogenous ANG II, PG, and antidiuretic hormone (ADH) release in seven normal volunteers before (control study) and after inhibition of PG synthesis by a single dose of aspirin (ASA study). In the control study, following the administration of 100 mg of C, there was a significant increase of plasma PGE2, plasma-renin activity (PRA), and urinary PGE2 and 6-keto-PGF1 alpha and a decrease of plasma ADH. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were unaffected by C; urine output, fractional sodium excretion (FENa), and osmolal clearance (Cosmol) increased; and urinary osmolality (Uosmol) decreased significantly after C. In the ASA study PG were undetectable in plasma and significantly reduced in urine 1 h after aspirin and did not increase when C was added. Plasma ADH decreased and PRA increased, as in the control study, after C, whereas GFR, RPF, urine output, FENa, Cosmol, and Uosmol were unchanged. These results suggest that the effect of C on ADH release may be mediated, to a large extent, by a fall in endogenous circulating ANG II, since ADH decreased in the presence of both high or undetectable levels of PGE2. The results also suggest that the increase in PGE2 induced by C may precipitate the diuretic and natriuretic effects of acute C administration.

Effects of truncated angiotensins in humans after double blockade of the renin system

“…Hollenberg et al (17) have shown that administration of captopril in healthy humans, on normal or restricted sodium diet, increases PRA and decreases plasma ANG II levels. A similar increase in PRA has been reported in humans on unrestricted sodium intake after inhibition of converting enzyme by captopril (33). However, these studies are difficult to compare with the present work due to differences in experimental design.…”

Effect of Exogenous Prostaglandin E₂ on Plasma Antidiuretic Hormone in Normal Man

“…In contrast, we did not observe an effect of endogenous PGE2 and of 6-keto-PGFic on plasma ADH in normal volunteers in whom these prostaglandins were stimu lated with angiotensin II [9] and captopril [10], Thus, while the role of endogenous PGE2 on the release of ADH is still unclear, it has been shown that high doses of exogenous vasodilator prostaglandins enhance the re lease of ADH in vitro [11,12] and in animals [13], but we do not know of studies in humans employing exoge nous PGE2 in order to evaluate their ability to increase plasma levels of ADH. The present study was therefore undertaken in the attempt to verify if exogenous PGE2 stimulates the central release of ADH also in normal man, as it occurs in laboratory experiments, but also in the attempt to clarify if other hormonal systems, in par ticular the renin-angiotensin system, play a role in the eventual PGE2-mediated increase in ADH, as suggested by previous findings [9,10]. For this purpose we mea sured plasma levels of ADH during the infusion of increasing doses of PGE2, both under basal conditions and after the inhibition of angiotensin II synthesis with captopril.…”

Effects of interrupting the renin‐angiotensin system on sodium excretion in man.

“…2 B) is consistent with the suggestion that captopril exerts its main effect on sodium excretion by increasing the rate at which sodium leaves the proximal tubule to enter the loop of Henle and, subsequently, the urine. Adams, 1977;Usberti et al 1986) or actually cause it to decrease (Hollenberg et al 1981). However, captopril had a profound effect on the excretion of filtered lithium.…”

“…These experiments would be consistent with a direct, receptor-mediated effect of endogenous angiotensin II in increasing sodium reabsorption by the proximal tubule. Nevertheless, it has been reported that the natriuresis caused by captopril in man can be abolished by aspirin (Usberti et al 1986), raising the possibility that cyclooxygenase products are involved as intermediates. Consequently, the precise mechanism by which captopril acts on the proximal tubule to reduce sodium reabsorption in man has yet to be established.…”

“…It is not known to what extent any of these intrarenal processes, documented by clearance, micropuncture and microperfusion techniques, contribute to the final natriuresis caused by blocking the action of endogenous angiotensin in the intact animal. In man, it is known that administration of converting enzyme inhibitors increases sodium excretion (MacGregor, Markandu, Roulston, Jones & Morton, 1980;Hollenberg, Meggs, Williams, Katt, Garnic & Harrington, 1981;Usberti et al 1986) but, beyond the possible involvement of cyclooxygenase products (Usberti et al 1986), the intrarenal mechanism of this natriuresis has not been studied. Consequently, the present study set out to examine the effects of disrupting the renin-angiotensin system on the lithium-and solute-free water clearances of normal volunteers over a wide range of dietary sodium.…”