Calcium- and endothelial-mediated vascular smooth muscle relaxation in rabbit aorta.
The role of calcium in the relaxations evoked by methacholine and A23187 in intact rabbit aortic rings was investigated. Methacholine (10(-8) to 10(-6) M) and the calcium ionophore A23187 (10(-8) to 10(-6) M) produced dose-dependent relaxations of rings which had been contracted with the alpha-adrenergic agonist phenylephrine. The ability of a ring to relax in this manner was correlated with the presence of endothelium as judged by transmission and scanning electron microscopy. Purposely disrupting the endothelium led to a loss of the relaxation response. In these rings methacholine caused dose-dependent contractions at concentrations greater than 10(-7) M. Deletion of Ca++ from the incubation medium inhibited maximum methacholine-induced relaxations by 67% and A23187-induced relaxations by 92%. The Ca++-channel blockers verapamil (10 microM) and nifedipine (0.5 microM) inhibited maximum methacholine-induced relaxations by 39% and 45%, respectively. The blockers had no effect on the methacholine ED50 (2.5 x 10(-7) M) for relaxation. Verapamil and nifedipine also inhibited maximum A23187-induced relaxations by 43% and 47% with no effect on the ED50 (6 x 19(-8) M) for relaxation. A structurally dissimilar vasodilator, sodium nitroprusside (10(-7) M), had no effect on the A23187-induced relaxation. These data are consistent with a role of Ca++ in regulating either the production or release of endothelial-derived relaxing factor(s).
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D007473:Ion Channels; D008688:Methacholine Compounds; D010656:Phenylephrine; D000001:Calcimycin; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium