[Age-related alteration of inhibitory effects of isradipine on alpha 1-adrenoceptor mediated responses].

We studied age-related alteration of inhibitory effects of a Ca2+ channel antagonist, isradipine, on alpha 1-adrenoceptor mediated responses in 6-, 10-, and 40-week-old rats. Age-related changes were observed in the inhibitory effects of isradipine on the norepinephrine-induced maximum contractions in the isolated thoracic aorta, the amplitude of the Ca(2+)-evoked increase of intracellular Ca2+ concentration and sustained contraction in fura-2-loaded preparations and the maximum number of binding sites (Bmax) of [3H] (+)-isradipine to aortic membranes. The dissociation constant (KD) of [3H] (+)-isradipine did not alter with age. In anesthetized rats, isradipine inhibited the dose-response curves of norepinephrine on the blood pressure in 6- and 40-week-old animals more effectively than those in 10-week-old animals. An inverse relationship between the potency of norepinephrine in the isolated thoracic aorta, the inhibitory effects of isradipine on the norepinephrine-induced maximum contractions and the logarithm of Bmax obtained in the [3H] (+)-isradipine binding experiment were found. These results suggest that the age-related alteration of inhibitory effects of isradipine on alpha 1-adrenoceptor mediated contractile responses and the increase of blood pressure are due to changes in the alpha 1-adrenoceptor density and the population of voltage-dependent L-type Ca2+ channels, rather than changes in the affinity of drug to the alpha 1-adrenoceptor or Ca(2+)-sensitivity of contractile elements of aortic smooth muscle.