Previously we have reported an increased renal a,-and /3-adrenergic receptor expression in male spontaneously hypertensive rats that occurred ontogeneticalry 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 a-subunits of the G proteins G, (G, ,,"," and G, t^), G,, 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 WistarKyoto rats; additionally, 28-week-old female normotensive and spontaneously hypertensive rats were studied. During ontogenesis of male normotensive rats, G, &" increased, G, r emained unchanged, and G^ and G,,, decreased. In adult normotensive rats no sex differences were detected for G, ^^, G, k.,, and G^. When male rats from the normotensive and T he kidney is the tissue with the greatest long-term impact on blood pressure control because of its infinite gain mechanism. 1 On the other hand, chronically elevated arterial blood pressure affects renal function.2 -3 Renal function is tightly controlled by neurotransmitters and hormones such as catecholamines, angiotensin II, endothelin, vasopressin, and neuropeptide Y, many of which act via G proteins. -6 We have recently reported that in parallel with blood pressure elevations numbers of a t -, a 2 -, and /3-adrenergic receptors increase in kidneys of spontaneously hypertensive rats (SHR) relative to those of age-matched normotensive Wistar-Kyoto (WKY) rats.7 Despite increased a r and /3-adrenergic receptor numbers, norepinephrine-stimulated inositol phosphate formation and isoprenaline-stimulated cyclic AMP (cAMP) formation remained unchanged.7 These data suggest the occurrence of a relative desensitization of renal a r and £-adrenergic receptors during the development of hypertension in SHR./3-Adrenergic receptor coupling to cAMP formation by adenylate cyclase occurs via the stimulatory G protein G, and can be attenuated via the inhibitory G protein G ; .8 aj-Adrenergic receptor coupling to inositol phosphate formation appears to occur via G q and/or G n 9 ; additionally, one or more subtypes of a^-adrenergic receptors may couple to inositol phosphate formaReceived October 21, 1993; accepted in revised form January 24, 1994.From the Department of Medicine, University of Essen, Germany.Correspondence to Dr Martin C. Michel, Nephrol. Lab. IG 1, Klinikum, Hufelandstr 55, D-45122 Essen, Germany. spontaneously hypertensive strains were compared, all G protein a-subunits were similar in the prehypertensive phase (3 weeks). In established hypertension (28 weeks), G, ,"", and G,,, were reduced, whereas G, &,« and G^ remained unchanged. G, fco, was also reduced during the development of hypertension (6 and 8 weeks), whereas G, ^ and G^, were not consistently altered in this phase. The reduction in G, ^^ seen in male adult hypertens...

Neuropeptide Y (NPY) content, NPY receptors, and alpha-subunits of the G proteins Go and Gi were determined in cerebral cortex of male normotensive Wistar-Kyoto and spontaneously hypertensive rats at 3-28 wk of age and of adult female rats. NPY lacked major effects on adenylate cyclase or inositol phosphate formation. NPY content was similar in all normotensive groups but lower in spontaneously hypertensive rats at all ages. 125I-NPY labeled a homogeneous population of Y1-like receptors. The Y1 NPY receptor number gradually increased with age with similar values in both strains but was significantly smaller in female than in male rats. The Y1 NPY receptor affinity was similar in all male groups but greater in female rats. The abundance of immunodetectable Go alpha and Gi alpha and of pertussis toxin substrates was less at 3 wk than in older rats but similar in both sexes and strains. We conclude that rat cerebral cortex contains Y1-like receptors; sex, age, and blood pressure differentially regulate NPY content, Y1 NPY receptors, and Go alpha and Gi alpha.