Effects of nitrendipine (BAY e 5009), nifedipine, verapamil, phentolamine, papaverine, and minoxidil on contractions of isolated rabbit aortic smooth muscle.
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.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008914:Minoxidil / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology*; D009568:Nitrendipine; D009638:Norepinephrine / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology*
D000959:Antihypertensive Agents; D011725:Pyridines; D008914:Minoxidil; D009568:Nitrendipine; D014700:Verapamil; D010208:Papaverine; D009543:Nifedipine; D011188:Potassium; D009638:Norepinephrine; D010646:Phentolamine