Potentiation by trandolaprilat of the endothelium-dependent hyperpolarization induced by bradykinin.
In canine coronary arteries, bradykinin evokes endothelium-dependent relaxations that are mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The converting-enzyme inhibitor trandolaprilat potentiates the endothelium-dependent relaxations evoked by bradykinin in this tissue. The present experiments were designed to determine whether or not facilitated release of EDHF contributes to the augmented response to bradykinin in the presence of trandolaprilat. Organ-chamber studies were performed to measure changes in isometric tension in rings of canine coronary arteries. In the presence of nitro-L-arginine, an inhibitor of NO synthase, trandolaprilat augmented the endothelium-dependent relaxations evoked by bradykinin. These relaxations were not inhibited by the K(+)-channel inhibitors tetraethylammonium, 4-aminopyridine, or glibenclamide, but were abolished in high-potassium solution. The membrane potential in individual smooth-muscle cells of coronary artery was measured by means of glass microelectrodes. Trandolaprilat potentiated the endothelium-dependent hyperpolarizations evoked by a subthreshold concentration of bradykinin, and these endothelium-dependent hyperpolarizations were inhibited by high-potassium solution. These experiments demonstrate that EDHF contributes to the relaxation evoked by bradykinin in the canine coronary artery and that trandolaprilat potentiates the release of this factor. This effect of trandolaprilat may contribute to its vasodilator properties.
Illiano
S
S
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas.
Mombouli
J V
JV
Nagao
T
T
Vanhoutte
P M
PM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D004285:Dogs; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D001685:Biological Factors; D007211:Indoles; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; C061095:trandolaprilat; D001920:Bradykinin