Inhibition of Norepinephrine Contractions by Diltiazem on Aorta and Pulmonary Artery from Young and Aged Rats: Influence of

Inhibition of contractile responses to norepinephrine by either diltiazem (1 M) or by reducing the extracellular calcium (from 2.5-0.25 mM) has been examined on isolated ring preparations of aorta and pulmonary artery from young (2 months old) and aged (1 9-21 months old) rats. On aorta, the reduction in the norepinephhne maximum contraction by diltiazem was signifi-candy greater in aged rats (40 % reduction) than in young rats (1 2 % reduction). The results obtained by reducing the extracel-lular calcium were indistinguishable from those with diltiazem (reduction in norepinephnne maximum: aged, 55%; young, 19%). The potency (negative log EC) of norepinephnne was less in aorta from aged than from young rats. This was not due to a lower affinity(pKA)of norepinephnne for the alpha adrenoceptors, but to a reduced alpha adrenoceptor reserve for norepinephnne. On pulmonary artery none of the above age-related changes was seen. It is concluded that, in aorta from aged rats, the inhibitory effect of diltiazem on norepinephnne-induced contrac-tions is enhanced, and that this is due to the age-related reduc-tion in alpha adrenoceptor reserve in this vessel. Age is one of the factors which can influence the response of the vasculature to drugs (Docherty, 1986), and there are several drugs for which this has now been demonstrated. These include a’pha adrenoceptor agonists (Cohen and Berkowitz, 1976