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.
Wanstall
J C
JC
Pharmacology Section, Department of Physiology and Pharmacology, University of Queensland, St Lucia, Brisbane, Australia.
O'Donnell
S R
SR
D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*; D014661:Vasoconstriction / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D004110:Diltiazem; D009638:Norepinephrine