Inhibition of norepinephrine contractions by diltiazem on aorta and pulmonary artery from young and aged rats: influence of alpha-adrenoceptor reserve.

Inhibition of contractile responses to norepinephrine by either diltiazem (1 microM) 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 (19-21 months old) rats. On aorta, the reduction in the norepinephrine maximum contraction by diltiazem was significantly greater in aged rats (40% reduction) than in young rats (12% reduction). The results obtained by reducing the extracellular calcium were indistinguishable from those with diltiazem (reduction in norepinephrine maximum: aged, 55%; young, 19%). The potency (negative log EC50) of norepinephrine was less in aorta from aged than from young rats. This was not due to a lower affinity (pKA) of norepinephrine for the alpha adrenoceptors, but to a reduced alpha adrenoceptor reserve for norepinephrine. 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 norepinephrine-induced contractions is enhanced, and that this is due to the age-related reduction in alpha adrenoceptor reserve in this vessel.