Properties of the ventricular adrenergic signal transduction system during ontogeny of spontaneous hypertension in rats.
The purpose of this study was to characterize adrenergic receptors and associated G proteins in ventricles of spontaneously hypertensive rats (SHRs) at different stages of development. The beta- and alpha1-adrenoceptor densities and subtype distribution, and beta-adrenoceptor-G protein coupling were studied by radioligand binding, and levels of G(Salpha), G(ialpha), and G(q/11alpha) protein species were determined by Western blotting in SHRs and Wistar-Kyoto (WKY) control rats aged 3.5 weeks, 3 months, and 8 months. In 3.5-week-old SHRs, both the beta-adrenoceptor density and the percentage of agonist high-affinity binding sites were higher than in age-matched WKY rats. The beta1/beta2-subtype distribution, the alpha1-adrenoceptor density, and the alpha1B/alpha1A-subtype distribution were similar in rats of both strains at all ages. Although essentially no differences in G(salpha) levels between SHRs and WKY rats were detected, higher G(ialpha) and lower Gq/1alpha concentrations were found in 3.5-week-old SHRs. In 3-month-old SHRs, increased levels of Gq/11alpha proteins were observed. In 8-month-old SHRs, none of the parameters was different from those of controls. We conclude that the differences in properties of the adrenergic signal transduction system between SHRs and WKY rats are exclusively observable before and at the onset of the overt hypertension. Moreover, the hypertensive genotype apparently affects G proteins more readily than adrenoceptors.
Bazan
A
A
Ghent University, Medical School, Heymans Institute of Pharmacology, Belgium.
Van de Velde
E
E
de Paepe
B
B
Fraeyman
N
N
D000818:Animals; D006352:Heart Ventricles; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D015151:Immunoblotting; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction; D016276:Ventricular Function
D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta