title: Endothelium-derived hyperpolarizing factor(s) and the potentiation of kinins by converting enzyme inhibitors.
abstract: Inhibitors of angiotensin converting-enzyme (ACE) enhance the endothelium-dependent relaxation to bradykinin and cause the accumulation of kinins in the vascular wall. Bradykinin elicits the production of vasodilator prostanoids and nitric oxide by endothelial cells. However, there is an additional component to the dilator actions of bradykinin, which is mediated by a diffusible endothelium-derived hyperpolarizing factor (EDHF). The knowledge gathered on the nature of EDHF and its mechanism of action are reviewed briefly. EDHF causes hyperpolarization and relaxation of arterial smooth muscle by activating K(+)-channel, the nature of which varies between species. During the inhibition of both cyclooxygenase and nitric oxide synthase, concentration-response relationships of the hyperpolarization and relaxation elicited by bradykinin overlap in canine coronary arteries. Both effects are enhanced equally by the ACE inhibitor perindoprilat. They are inhibited by membrane depolarization that is obtained by raising the extracellular concentrations of potassium ions. Likewise, in the human coronary artery, the hyperpolarization elicited by bradykinin, which is also mediated by EDHF, is augmented in the presence of perindoprilat and prevented by potassium-induced depolarization. In this blood vessel, contrary to the canine coronary artery, the EDHF-mediated responses occur at concentrations comparable to those initiating the nitric oxide-dependent component. Therefore, the increased production of EDHF, which is induced by kinins, may contribute to the cardiovascular effects of perindoprilat, together with an enhanced production of nitric oxide and vasodilator prostanoids.
authors.affiliation: Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: Mombouli
authors.forename: P M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007705:Kinins / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D009569:Nitric Oxide