Evidence for an age-dependent functional expression of alpha 1D-adrenoceptors in the rat vasculature.
The role of the alpha 1-adrenoceptor subtypes, and their possible change with maturation, in alpha 1-adrenoceptor-induced pressor responses in the rat has not been established. Thus, the effects of the alpha 1D-, alpha 1A/1D- and alpha 1B/1D-adrenoceptor antagonists, BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl) 8-azaspiro (4.5) decane-7,9-dione 2HCl), 5-methyl-urapidil and chloroethylclonidine, respectively, on the pressor responses induced by phenylephrine in 1- and 5-month-old pithed rats were investigated. The pressor responses induced by phenylephrine were competitively antagonized by both BMY 7378 and chloroethylclonidine in 5-month-old, but not in young immature animals; in marked contrast, 5-methylurapidil antagonized with similar potency the phenylephrine-induced pressor responses in animals of both ages. The present pharmacological data suggest that functional expression of alpha 1D-adrenoceptors in the rat resistance vessels increases with age; alpha 1A-, but not alpha 1B- or alpha 1D-adrenoceptors, seem to predominate in immature animals. These findings represent the first evidence that age-related changes in functional alpha 1-adrenoceptor subtypes occur in the systemic vasculature in vivo.
Ibarra
M
M
Departamento de Farmacología y Toxicología, CINVESTAV-IPN, México, D.F., Mexico.
Terrón
J A
JA
López-Guerrero
J J
JJ
Villalobos-Molina
R
R
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000378:metabolism*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; D010656:Phenylephrine; C051731:chlorethylclonidine; C053428:BMY 7378; D003000:Clonidine