ACE inhibitors potentiated bradykinin-induced endothelium-dependent relaxations in canine coronary arteries by enhancing both nitric oxide release and endothelium-derived hyperpolarizing factor.
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-ArgHyp3,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 et al. (Wed,) conducted a other in Canine coronary artery physiology. ACE inhibitors (cilazaprilat and perindoprilat) vs. Control (absence of ACE inhibitors) was evaluated on Isometric tension, tissue levels of cGMP, and transmembrane potential. ACE inhibitors potentiated bradykinin-induced endothelium-dependent relaxations in canine coronary arteries by enhancing both nitric oxide release and endothelium-derived hyperpolarizing factor.