Alpha 1-adrenoceptor responsiveness in the aging aorta.
Previous studies from this laboratory have shown that aortic alpha 1-adrenoceptor-mediated responsiveness is altered during maturation and aging. This study examines the possibility that there is a change in the alpha 1-adrenoceptor subtypes in the aorta during maturation and aging. The apparent affinity of norepinephrine, as determined by partial receptor inactivation with the alpha 1-adrenoceptor antagonist phenoxybenzamine, was found to be higher in 1-month-old rats compared to 6- and 24-month-old rats. The alpha 1B-adrenoceptor subtype-selective antagonist chlorethylclonidine was used to examine possible heterogeneity in aortic alpha 1-adrenoceptors. The inhibitory effect of chlorethylclonidine on norepinephrine-stimulated contraction was greater in young animals compared to aged animals. Chlorethylclonidine blocked norepinephrine-stimulated inositol phosphate accumulation in 1-month-old aorta but it produced only partial inhibition in the 6- and 24-month-old aortas. The relatively non-selective alpha 1-adrenoceptor antagonists phenoxybenzamine (0.1 microM) and prazosin (0.1 microM) inhibited inositol phosphate accumulation and contractile responses in all ages. The complete block of alpha 1-adrenoceptor-mediated responses by chlorethylclonidine in younger animals shows that alpha 1-adrenoceptor-mediated responses are mediated by the chlorethylclonidine-sensitive alpha 1-adrenoceptor subtypes. The partial inhibition by chlorethylclonidine of alpha 1-adrenoceptor-mediated responses in 6- and 24-month-old animals indicates an increased role of an alpha 1-adrenoceptor subtype that is relatively insensitive to chlorethylclonidine.
Gurdal
H
H
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Cai
G
G
Johnson
M D
MD
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001667:Binding, Competitive; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D007295:Inositol Phosphates; D018340:Receptors, Adrenergic, alpha-1; D010643:Phenoxybenzamine; C051731:chlorethylclonidine; D003000:Clonidine; D009638:Norepinephrine