Effect of Felodipine, a New Dihydropyridine Vasodilator, on Contractile Responses to Potassium, Noradrenaline, and Calcium in Mesenteric Resistance Vessels of the Rat

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Abstract
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 Ca. Felodipine (10-15-10-9 M) had a concentration-dependent inhibitory action on contraction induced by maximal K (125 mM) and noradrenaline [norepinephrine] (10-5 M) stimulation. Felodipine was more potent and more selective than D600 [methoxyverapamil] and nifedipine. K and noradrenaline concentration-response characteristics were insurmountably antagonized by felodipine, the K sensitivity of vessels being unaffected while noradrenaline sensitivity was decreased. In Ca-depleted vessels, felodipine in all concentrations tested produced insurmountable antagonism of the K-activated Ca 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 K-activated vessels almost completely, whereas .apprx. 50% of the response of noradrenaline-activated vessels persisted. The effect of felodipine may be caused primarily by selective inhibition of responses evoked by membrane depolarization.