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Effects of nitrendipine (BAY e 5009), nifedipine, verapamil, phentolamine, papaverine, and minoxidil on contractions of isolated rabbit aortic smooth muscle


, : Effects of nitrendipine (BAY e 5009), nifedipine, verapamil, phentolamine, papaverine, and minoxidil on contractions of isolated rabbit aortic smooth muscle. Journal of Cardiovascular Pharmacology 4(6): 895-902

The effects of nitrendipine, a new antihypertensive agent, have been examined using the isolated rabbit aortic strip stimulated with either noradrenaline (1.7 X 10(-8) - 1.7 X 10(-5) mol/L) or potassium (22.7-52.7 mmol/L). Nifedipine, verapamil, phentolamine, papaverine, and minoxidil were used as reference compounds. Nitrendipine and nifedipine had little effect on the contractions of the aortic strip induced by noradrenaline, but concentration-dependently inhibited contractions induced by potassium depolarisation (IC50) (3.1 X 10(-9) and 8.1 X 10(-9) mol/L, respectively). Verapamil had little effect on contractions induced by the highest concentration of noradrenaline (1.7 X 10(-5) mol/L) but inhibited contractions induced by lower concentrations of noradrenaline. Potassium-induced contractions were inhibited with an IC50 of 1.4 X 10(-7) mol/L. Phentolamine competitively inhibited noradrenaline-induced contractions, but had no effect on those induced by potassium. Papaverine inhibited both noradrenaline- and potassium-induced contractions with an IC50 of 2.5 X 10(-5) and 3 X 10(-5) mol/L, respectively. Minoxidil also inhibited both types of contractions, but only at very high concentrations (IC50 1.3 X 10(-3) and 1.8 X 10(-3) mol/L). I conclude that nitrendipine, like nifedipine, acts by inhibiting the depolarisation-induced influx of calcium ions into the vascular smooth muscle. There is no evidence for alpha-adrenoceptor-blocking activity, nor for papaverine-like vasodilator activity. Verapamil also appears to act by a calcium antagonistic action; but may, in addition, possess some alpha-adrenoceptor-blocking activity.

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PMID: 6185780


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