Calmidazolium, a calmodulin inhibitor, inhibits endothelium-dependent relaxations resistant to nitro-L-arginine in the canine coronary artery.
1. The role of calmodulin in endothelium-dependent relaxations in the canine coronary artery, was investigated by use of the inhibitor of calmodulin, calmidazolium. 2. The endothelium-dependent relaxations to adenosine diphosphate (ADP) and nebivolol, a beta-adrenoceptor antagonist, in control solution, and to bradykinin in high potassium solution (to inhibit endothelium-dependent hyperpolarization), were abolished by nitro-L-arginine (30 microM), an inhibitor of nitro oxide-synthase. Calmidazolium (10 microM) did not inhibit these relaxations. 3. Calmidazolium did not affect the endothelium-independent relaxations to SIN-1, an exogenous donor of nitric oxide (NO). 4. The relaxations to bradykinin and to the calcium ionophore A23187 in control solution were inhibited to a small extent by calmidazolium (10 microM). 5. Bradykinin and A23187 induced relaxations in the presence of nitro-L-arginine (30 microM) that were abolished by calmidazolium (10 microM) but not affected by glibenclamide (10 microM), an inhibitor of ATP-sensitive K+ channels. 6. The endothelium-independent relaxations to lemakalim, an ATP-sensitive K+ channel opener, were not affected by calmidazolium (10 microM) but were inhibited by glibenclamide (10 microM). 7. These results suggest that calmidazolium does not inhibit the endothelium-dependent relaxations due to endothelium-derived NO in the canine coronary artery but inhibits either the production of endothelium-derived hyperpolarizing factor (EDHF) from endothelial cells or its effects on vascular smooth muscle cells. Furthermore these results suggest that EDHF contributes to endothelium-dependent relaxations in the canine coronary artery.
Illiano
S
S
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, TX 77030.
Nagao
T
T
Vanhoutte
P M
PM
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D019806:Cromakalim; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D004983:Ethanolamines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D000068577:Nebivolol; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D011758:Pyrroles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D002147:Calmodulin; D004983:Ethanolamines; D007093:Imidazoles; D011758:Pyrroles; D014665:Vasodilator Agents; D000068577:Nebivolol; D019806:Cromakalim; D019335:Nitroarginine; D009569:Nitric Oxide; D000001:Calcimycin; C031938:calmidazolium; D000244:Adenosine Diphosphate; D001120:Arginine; D001920:Bradykinin