Vasodepressor Property of the Converting Enzyme Inhibitor Captopril (SQ 14 225): The Role of Factors other than Renin-Angiotensin Blockade in the Rat

Abstract

1. The peptide converting enzyme inhibitor captopril was given (1.25 mg/kg intravenously) to normal and nephrectomized rats and rats with renovascular and deoxycorticosterone hypertension. 2. Captopril lowered blood pressure to a small extent in normal and nephrectomized rats. Bradykinin infusion in nephrectomized animals, however, potentiated the vasodepressor action of captopril. 3. Captopril produced a major blood pressure fall in the early stages of Goldblatt two-kidney one-clip hypertension: even when hypertension had been present for more than 4 months, a substantial vasodepressor action was seen. Rats with deoxycorticosterone-induced hypertension also showed a significant blood pressure fall. 4. Captopril was given to salt-loaded and salt-depleted rats in which the renin-angiotensin system had been blocked by infusion of the competitive angiotensin II antagonist saralasin. Captopril still lowered blood pressure in the salt-depleted group. 5. Captopril lowers blood pressure in situations where the renin-angiotensin system is not responsible for blood pressure maintenance. Further, the fall in blood pressure produced in Goldblatt two-kidney one-clip hypertension is greater than would be predicted on the basis of renin-angiotensin blockade. It is likely therefore that captopril lowers blood pressure by an action additional to angiotensin blockade. Bradykinin potentiation is one possible mechanism by which this may take place.

Inhibition of bradykinin‐induced vasodilation in human forearm vasculature by icatibant, a potent B2‐receptor antagonist.

“…Local ACE inhibition not only blocks the constrictor effect of angiotensin I but also enhances the dilator response to bradykinin in the human forearm [10,27]. ACE inhibitors are effective in experimental and human hypertension in circumstances when circulating renin is low or normal [28][29][30][31], and it has been suggested that the hypotensive response to ACE inhibition may be mediated in part by potentiation of bradykinin either in the circulation or tissues [32]. Animal studies have shown that a bradykinin antagonist (B4147) that is less potent than icatibant can blunt the hypotensive response to ACE inhibition by approximately 40% [33].…”

Reversal by angiotensins II and III of the effects of converting enzyme inhibition on renal electrolyte excretion in rats.

“…Converting enzyme inhibitors such as Captopril and Teprotide may raise intrarenal concentrations of bradykinin and prostaglandins (Marks, Bing, Thurston & Swales, 1980) which may then be responsible for changes in renal function. At present, however, the weight of evidence favours the proposal that the renal responses are largely due to decreased angiotensin II (A II) production (Hollenberg, 1982 (Freeman, Davis, Lohmeier & Spielman, 1977), infusion of this analogue would also be expected to reverse the actions of Teprotide.…”

Preventive Effect of Angiotensin I on Weight Reduction in the Adrenal Glands of DOCA/salt Hypertensive Rats.

“…It has been reported, however, that the hypotensive effect of CEI is due not only to the blockade of angiotensin converting enzyme but also to stimulation of prostaglandin synthesis (Barr et al, 1980), an increase in kinin (Marks et al, 1980) and a reduction of vasopressin (Igarashi et al, 1985). Thus, such mechanisms might have induced a decrease in B. P. in the present study.…”