title: Alteration of alpha1-adrenoceptor subtypes in aortas of 12-month-old spontaneously hypertensive rats.
abstract: Alterations in alpha1-adrenoceptor subtypes in aortas from 12-month-old spontaneously hypertensive rats (SHR) were studied in functional studies and RNase protection assays. The norepinephrine-induced contraction, including maximum response and pD2 values, was not significantly different between the SHR and age-matched Kyoto Wistar (WKY) rats. The pA2 values of the alpha1D-adrenoceptor subtype-selective antagonist BMY7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)dec ane-7,9-dionedihydrochloride) were increased from 8.10 +/- 0.12 in WKY rats to 8.45 +/- 0.13 in SHR (P < 0.05). The pA2 values of the alpha1A-adrenoceptor subtype-selective antagonist RS-17053 (N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha,alpha-dim ethyl-1H-indole-3-ethanamine hydrochloride) were reduced from 8.52 +/- 0.20 in WKY rats to 7.82 +/- 0.18 in SHR (P < 0.05), whereas the pA2 values of the alpha1A/alpha1D-adrenoceptor subtype-selective antagonist WB4101 (2-(2,6-dimethoxphenoxyethyl)-aminomethyl-1,4 benzodioxane) were not significantly different between WKY rats and SHR (9.05 +/- 0.22 versus 9.27 +/- 0.15, P > 0.05). Preincubation of preparations in 50 microM chloroethylclonidine for 30 min irreversibly inhibited the norepinephrine-induced response more profoundly in aortas from SHR than in aortas from WKY rats. The results of RNase protection assays showed that mRNAs for alpha1A- and alpha1B-adrenoceptor subtypes were decreased and that mRNA for the alpha1D-adrenoceptor subtype was increased in aortas from SHR compared with WKY rats. The results suggested that the alpha1A-adrenoceptor subtype was decreased and the alpha1D-adrenoceptor subtype was increased in aortas of 12-month-old SHR.
authors.affiliation: Institute of Vascular Medicine, Third Hospital, Beijing Medical University, PR China.
authors.forename: K
authors.initials: K
authors.lastname: Xu
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.forename: H
authors.initials: H
authors.lastname: Wei
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Han
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000502:physiology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007211:Indoles; D010879:Piperazines; C099495:RS 17053; D018340:Receptors, Adrenergic, alpha-1; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D012260:Ribonucleases; C053428:BMY 7378; D003000:Clonidine; D009638:Norepinephrine