Effect of felodipine, a new dihydropyridine vasodilator, on contractile responses to potassium, noradrenaline, and calcium in mesenteric resistance vessels of the rat.
The effect of felodipine [4-(2,3-dichloro-phenyl)-1,4-dihydro-2,6-dimethyl-3-ethoxycarbonyl-5- methoxycarbonylpyridine on the contractile responses of mesenteric resistance vessels denervated in vitro was investigated. Sustained contractions of this vessel type were totally dependent on extracellular calcium. Felodipine (10-(15)-10-(9)M) had a concentration-dependent inhibitory action on contraction induced by maximal potassium (125 mM) and noradrenaline (10-(5)M) stimulation. Felodipine was more potent and more selective than D600 and nifedipine. Potassium and noradrenaline concentration-response characteristics were insurmountably antagonized by felodipine, the potassium sensitivity of vessels being unaffected while noradrenaline sensitivity was decreased. In calcium-depleted vessels, felodipine in all concentrations tested produced insurmountable antagonism of the potassium-activated calcium concentration-response characteristics, whereas the antagonism in low concentrations (10-(15)-10-(11)M) was surmountable in noradrenaline-activated vessels. Felodipine 10-(9) M blocked the response of potassium-activated vessels almost completely, whereas approximately 50% of the response of noradrenaline-activated vessels persisted. The results of this investigation indicate that the effect of felodipine may be caused primarily by selective inhibiton of responses evoked by membrane depolarization.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003714:Denervation; D015736:Felodipine; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D005711:Gallopamil; D009543:Nifedipine; D015736:Felodipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine