Potentiation of endothelium-dependent relaxations to bradykinin by angiotensin I converting enzyme inhibitors in canine coronary artery involves both endothelium-derived relaxing and hyperpolarizing factors.
Studies were designed to investigate the mechanisms underlying the augmentation by angiotensin I converting enzyme (ACE) inhibitors of the endothelium-dependent relaxations evoked by bradykinin. Isometric tension, tissue levels of cGMP, and transmembrane potential were measured in isolated canine coronary arteries as indications of the respective contribution of nitric oxide and endothelium-derived hyperpolarizing factor. In rings of coronary artery with endothelium, relaxations to bradykinin were potentiated by the ACE inhibitors cilazaprilat and perindoprilat. NG-Nitro-L-arginine (NLA), a nitric oxide synthase inhibitor, impaired relaxations to bradykinin. But the presence of ACE inhibitors partially restored this activity. Bradykinin stimulated the production of cGMP, and this was enhanced significantly by ACE inhibitors, indicating an augmented release of nitric oxide. NLA abolished the increase induced by bradykinin irrespective of the presence of ACE inhibitors. Electrophysiological studies revealed that bradykinin elicited an endothelium-dependent hyperpolarization of vascular smooth muscle that was insensitive to NLA and potentiated by ACE inhibitors. The bradykinin-induced hyperpolarization and NLA-resistant relaxations were transient and impaired by potassium depolarization. Thus, production of endothelium-derived hyperpolarizing factor may account for the NLA-resistant relaxations of canine coronary arteries. The relaxations induced by bradykinin were unaffected by the B1 kinin receptor antagonist des-Arg9,[Leu8]-bradykinin either in the absence or in the presence of NLA but were antagonized by the B2 kinin receptor antagonist D-Arg[Hyp3,D-Phe7]-bradykinin. Molecular exclusion chromatography of 125I-labeled [Tyr8]-bradykinin and its degradation products demonstrated that the breakdown of the kinin by isolated coronary arteries was prevented in the presence of perindoprilat.(ABSTRACT TRUNCATED AT 250 WORDS)
Mombouli
J V
JV
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Tex.
Illiano
S
S
Nagao
T
T
Scott-Burden
T
T
Vanhoutte
P M
PM
D000803:Angiotensin I / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D014664:Vasodilation
D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide; D000803:Angiotensin I; D006152:Cyclic GMP; D001920:Bradykinin