Endothelium-mediated vasodilation during ACE inhibition

Abstract

ACE inhibitors are superior to other vasodilators in the treatment of congestive heart failure and may be advantageous in patients with myocardial infarction and hypertension. The mechanisms mediating these beneficial effects are not clear. The present article discusses the mechanisms leading to augmented release of endothelium-derived nitric oxide during ACE inhibition. Acute potentiation of bradykinin (Bk)-induced vasodilation was studied in rings of bovine and human coronary arteries mounted in organ chambers for recording of isometric force. The ACE inhibitors captopril, enalaprilat, fosinoprilat, lisinopril, or ramiprilat alone did not affect vascular tone in isolated coronary tone in isolated coronary artery preparations with intact endothelium. However, in the presence of exogenous Bk, kallidin, or one of the slowly degradable Bk2-receptor agonists D-Arg(Hyp3)-Bk or [Hyp3-Tyr(Me)8]-Bk they elicited potent concentration-dependent relaxations. Relaxations in response to lisinopril were not observed in the presence of other vasodilators. They were prevented by mechanical removal of the endothelium, inhibition of nitric oxide synthase or Bk2-receptor blockade. The data indicate that ACE inhibitors potentiate the effects of Bk on endothelial cells by a local mechanism, probably independent of the degradation of bradykinin. The chronic effects of ACE inhibitors on endothelial function were compared with those of selective angiotensin(AT)1-receptor blockade in cyclosporin A (CsA) treated rats. Chronic AT blockade alone does not affect endothelium-dependent relaxation and increases contractions to ATII in the rot aorta. Combination of CsA with either an ACE-Inhibitor or an AT2 receptor antagonist prevented the endothelial dysfunction in the rat arta observed after CsA alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose‐dependent Effect of Captopril on Aortic Reactivity of Streptozotocin‐diabetic Rats

“…In contrast, captopril has been reported to diminish contractile responses to PE in the presence of a functional endothelium in normal rats that is not mediated through bradykinin receptors 31 . In this respect, it has also been shown that ACE inhibitors potentiate the effects of bradykinin on endothelial cells by a local mechanism, probably independent of the degradation of bradykinin 11 . Other findings indicate that the effects of captopril are mediated not only via inhibition of the formation of vasoconstrictory angiotensin II, but also by accumulation of bradykinin, which stimulates the synthesis of vasodilatory NO 30 .…”

“…31 In this respect, it has also been shown that ACE inhibitors potentiate the effects of bradykinin on endothelial cells by a local mechanism, probably independent of the degradation of bradykinin. 11 Other findings indicate that the effects of captopril are mediated not only via inhibition of the formation of vasoconstrictory angiotensin II, but also by accumulation of bradykinin, which stimulates the synthesis of vasodilatory NO. 30 Meanwhile, ACE inhibitors were not able to alter NO synthesis by vascular smooth muscle cells under basal and interleukin-1␤-stimulated conditions in cultured rat vascular smooth muscle cells.…”

“…Various experimental evidence supports the involvement of haemodynamic effects and/or the stimulation of cytoprotective prostaglandins 8 . The enhancement of bradykinin‐induced relaxation, 9,10 augmented release of endothelium‐derived nitric oxide, 11 decreased production of endothelin‐1 12 and a free radical‐scavenging action 13 have also been postulated. Renoprotective effects of some of the ACE inhibitors in streptozotocin (STZ)‐induced diabetes have also been reported in rats 14 .…”

Effects of angiotensin II receptor antagonist on endothelial vasomotor function and urinary albumin excretion in type 2 diabetic patients with microalbuminuria

“…In hypertensive type 2 patients with diabetic nephropathy, lisinopril has been shown to improve endothelial dysfunction [9]. The mechanisms whereby ACEI improve endothelial function may involve sparing of bradykinin by ACEI and an antioxidant effect via decreased angiotensin II-mediated production of superoxide anion by membrane-bound oxidases [10,11].…”

Losartan, an angiotensin type 1 receptor antagonist, improves conduit vessel endothelial function in Type II diabetes

“…The mechanisms responsible may involve sparing of bradykinin by ACE inhibitors [7][8][9][10][11][12], an antioxidant effect via decreased angiotensin II-mediated production of superoxide anion by membrane-bound oxidases [13][14][15] or other mechanisms [6]. Losartan, a drug which blocks angiotensin type 1 receptors, also improves resistance vessel endothelial function in subjects with Type II diabetes [16], suggesting that at least part of the beneficial effect of angiotensin II modulation is mediated through the angiotensin II\type 1 receptor pathway.…”