Interference of the Calcium Antagonist Nisoldipine with the Abnormal Response of Vessels from Hypertensive Rats to α‐Adrenergic Stimulation

The effects of the calcium antagonist nisoldipine on contractions stimulated by phenylephrine and B-HT 920 (agonists of α1- and α2-adrenoceptors) in isolated aortic rings from stroke-prone spontaneously hypertensive rats (SHRSP) and from normotensive Wistar-Kyoto rats (WKY) were investigated in vitro. Phenylephrine and B-HT 920 produced concentration-dependent contractions of vessels from both groups of animals. The absolute force of the contractions was less in the aortae from hypertensive rats after all doses of both agonists. Nisoldipine inhibited the B-HT 920-induced contraction much more in vessels from SHRSP than in those from normotensive WKY rats (IC50 = 1.5 x 10 10 versus 7 x 10-9 g/ml). The phenylephrine contractions were inhibited in SHRSP aortae by higher concentrations (IC50 −8.5 × 10 8 g/ml) of nisoldipine: in WKY, nisoldipine only produced a slight inhibition of phenylephrine-induced contractions. The inhibitory concentrations of nisoldipine on BHT-920-induced contractions are similar to those for the inhibition of the calcium or depolarization-induced contractions in other experiments. The α2-agonist-induced contractions of rat aorta are dependent on trans-membrane calcium supply. The higher efficacy of nisoldipine in aortae from SHRSP suggests an increased trans-membrane availability of calcium ions in hypertension.