We studied age-related alteration of inhibitory effects of a Ca
2+ channel antagonist, isradipine, on α
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 Ca
2+ concentration and sustained contraction in fura-2-loaded preparations and the maximum number of binding sites (B
max) of [
3H] (+)-isradipine to aortic membranes. The dissociation constant (K
D) 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 B
max obtained in the [
3H] (+)-isradipine binding experiment were found. These results suggest that the age-related alteration of inhibitory effects of isradipine on α
1-adrenoceptor mediated contractile responses and the increase of blood pressure are due to changes in the α
1-adrenoceptor density and the population of voltage-dependent L-type Ca
2+ channels, rather than changes in the affinity of drug to the α
1-adrenoceptor or Ca
2+-sensitivity of contractile elements of aortic smooth muscle.
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