Mechanisms of relaxant action of nicardipine, a new Ca++-antagonist, on isolated dog cerebral and mesenteric arteries.
In helically-cut strips of cerebral and mesenteric arteries contracted with prostaglandin (PG) F2 alpha, carbocyclic thromboxane A2 (cTxA2) or K+, the addition of nicardipine caused a dose-related relaxation. Nicardipine-induced relaxation was greater in cerebral than in mesenteric arteries when contracted with PGF2 alpha and cTxA2, but did not appreciably differ in the arteries contracted with K+. Cerebral arteries contracted with hemolysate and PGF2 alpha relaxed in response to nicardipine to a similar extent. The contractile response to PGF2 alpha was attenuated by pretreatment with nicardipine, the attenuation being greater in cerebral than in mesenteric arteries. Ca++-induced contractions in cerebral and mesenteric arteries previously exposed to Ca++-free media and depolarized by excess K+ were attenuated by nicardipine to a similar extent. PGF2 alpha-induced contractions of cerebral arteries exposed to Ca++-free media were attenuated by nicardipine, whereas those of mesenteric arteries were unaffected. Attenuations by nicardipine of the Ca++-induced contraction in PGF2 alpha-treated cerebral arteries were greater than those seen in mesenteric arteries. It may be concluded that nicardipine produces a greater relaxation of cerebral arteries than mesenteric arteries, possibly due to a greater inhibition of the Ca++-influx and to a decrease in the release of Ca++ from intracellular storage sites in cerebral arteries. As far as the concentrations used are concerned, nicardipine appears to attenuate the inward movement of Ca++ across cell membrane in mesenteric arterial smooth muscle, but not the release of intracellularly stored Ca++.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000378:metabolism
D011460:Prostaglandins F; D011725:Pyridines; D013928:Thromboxane A2; D009529:Nicardipine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium