Dihydropyridine calcium agonists selectively enhance resistance artery myogenic tone.
Upon stretch in normal physiological salt solution (PSS), two dihydropyridine (DHP) Ca2+ agonists (Bay k 8644 and CGP 28392) enhanced the level of stretch-dependent myogenic tone in rabbit ear resistance arteries. This potentiating effect was not blocked by phenoxybenzamine (1 microM) and was Ca2+-dependent. Bay k 8644 was more potent than CGP 28392. These agonists had a smaller potentiating effect on K+ (20 mM)-induced contraction, and had little effect in the presence of high K+ (50-134 mM) PSS. Stretch-dependent myogenic tone is resistant to the inhibitory effect of nimodipine, a selective DHP Ca2+ antagonist which inhibited K+ (50 mM)-induced contraction in the nanomolar range. The potentiating effects of Bay k 8644 and CGP 28392 on myogenic tone were reversed by nimodipine. Our data suggest that DHP Ca2+ agonists selectively enhance myogenic tone by a mechanism that is antagonized by nimodipine, although physiological activation of myogenic tone is nimodipine insensitive, and the calcium related mechanisms of myogenic tone are distinct from those for high K+ depolarization-induced tone.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*
D007473:Ion Channels; D011725:Pyridines; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C040525:CGP 28392; D011188:Potassium; D002118:Calcium