New dihydropyridine drug, nilvadipine, blocks the calcium slow action potential in rat-cultured aortic smooth muscle cells.
The effects of the dihydropyridine analogs, nilvadipine (FR-34235) and mesudipine, on the electrical activity of rat aortic smooth muscle cells in culture (reaggregates) were compared with the calcium antagonist verapamil. Nilvadipine blocked the tetraethylammonium-induced action potentials (APs), whose inward current is carried almost exclusively by Ca2+ through voltage-dependent slow channels. The effects of nilvadipine were dose dependent, and nilvadipine had a more potent inhibitory effect on the K+-induced contraction than on the norepinephrine-induced contraction of rabbit aorta. The ED50 value for blockade of the K+-induced contracture by nilvadipine was 6.4 X 10(-8) M, and complete blockade of the Ca2+ slow channels occurred at 10(-8) M. Mesudipine also inhibited the Ca2+ slow channels in cultured vascular smooth muscle cells in a dose-dependent manner; elevation of the [Ca]O from 1.8 to 5.4 mM partially restored the slow APs. The order of the inhibitory action on the Ca2+-dependent slow APs was: nilvadipine greater than mesudipine greater than verapamil. The inhibition of Ca2+ influx during excitation by the drugs can account for their vasodilatory properties.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011188:Potassium / Q000037:antagonists & inhibitors; D011817:Rabbits
D002121:Calcium Channel Blockers; C035100:nilvadipine; C036653:mesudipine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine