Influence of age on calcium entry blocking drugs in rat aorta is spasmogen-dependent.
On rat aorta, diltiazem (0.2 microM) caused parallel shifts in the Ca2+ concentration-response curves (K+-depolarized preparations). In aged (greater than 19 months) rats, this shift (0.57 log units) was smaller than in young (2 months) rats (1.04 log units) indicating an age-related reduction in the potency of diltiazem. Felodipine (10 nM), like diltiazem (1 microM) in a previous study, depressed the maximum response to noradrenaline more in preparations from aged rats (40% reduction) than from young rats (14% reduction). This increase in the effect of felodipine or diltiazem vs. noradrenaline reflected a reduction in the alpha-adrenoceptor reserve for noradrenaline. Accordingly, the depression in the maximum responses to other spasmogens (5-HT or K+) by 1 microM diltiazem was not increased by age (5-HT, young 59%, aged 49% reduction; K+, young 65%, aged 70% reduction). This aging can have two opposing influences on the effects of Ca2+ entry blocking drugs on rat aorta - a decrease in potency, yet an increase in effectiveness against spasmogens with a reduced receptor reserve.
Wanstall
J C
JC
Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Brisbane, Australia.
O'Donnell
S R
SR
D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology; D004347:Drug Interactions; D015736:Felodipine; D008297:Male; D009568:Nitrendipine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology
D002121:Calcium Channel Blockers; D012701:Serotonin; D009568:Nitrendipine; D004110:Diltiazem; D015736:Felodipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine