ONTOGENY OF SYMPATHETIC RESPONSIVENESS IN SPONTANEOUSLY HYPERTENSIVE RATS .2. RENAL G-PROTEINS IN MALE AND FEMALE RATS

Previously we have reported an increased renal alpha(1)- and beta-adrenergic receptor expression in male spontaneously hypertensive rats that occurred ontogenetically in parallel with blood pressure elevation. However, increased receptor numbers were not accompanied by enhanced stimulation of inositol phosphate and cyclic AMP formation, respectively, indicating relative desensitization. We have now quantified alpha-subunits of the G proteins G(s) (G(s short) and G(s long)), G(i), and G(q) by immunoblotting and pertussis toxin-catalyzed ADP-ribosylation in renal membranes from 3-, 6-, 8-, and 28-week-old normotensive and spontaneously hypertensive male Wistar-Kyoto rats; additionally, 28-week-old female normotensive and spontaneously hypertensive rats were studied. During ontogenesis of male normotensive rats, G(s short) increased, G(s long) remained unchanged, and G(i alpha) and G(q alpha) decreased. In adult normotensive rats no sex differences were detected for G(s short), G(s long), and G(i alpha). When male rats from the normotensive and spontaneously hypertensive strains were compared, all G protein alpha-subunits were similar in the prehypertensive phase (3 weeks). In established hypertension (28 weeks), G(s long) and G(q alpha) were reduced, whereas G(s short) and G(i alpha) remained unchanged. G(s long) was also reduced during the development of hypertension (6 and 8 weeks), whereas G(s short) and G(i alpha) were not consistently altered in this phase. The reduction in G(s long) seen in male adult hypertensive rats was not detectable in female hypertensive rats. We conclude that reduced G(s long) and G(q alpha) may explain the previously observed relative desensitization of adenylate cyclase and phospholipase C stimulation by beta- and alpha(1)-adrenergic receptors, respectively, in male spontaneously hypertensive rats. Additionally, our data indicate sex-specific differences in G protein signaling in kidneys from hypertensive rats.