Abstract

Hypertension in spontaneously hypertensive rats (SHRs) is due in part to enhanced effects of vasoactive peptides on the renal vasculature. We hypothesize that the G_i signal transduction pathway enhances renovascular responses to vasoactive peptides in SHRs more so than in normotensive Wistar-Kyoto (WKY) rats. To test this hypothesis, we examined in isolated perfused kidneys from SHRs and WKY rats the renovascular responses (assessed as changes in renal perfusion pressure in mm Hg) to angiotensin II (10 nM) and vasopressin (3 nM) in the presence and absence of UK-14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine; an agonist that selectively activates the G_i pathway by stimulating α₂-adrenoceptors]. In SHR, but not WKY, kidneys, UK-14,304 (10 nM) enhanced (P < 0.05) renovascular responses to angiotensin II (control WKY, 43 ± 6; UK-14,304-treated WKY, 52 ± 19; control SHR, 66 ± 17; UK-14,304-treated SHR, 125 ± 16) and vasopressin (control WKY, 42 ± 17; UK-14,304-treated WKY, 36 ± 11; control SHR, 16 ± 8; UK-14,304-treated SHR, 83 ± 17). Pretreatment of SHRs with pertussis toxin (30 μg/kg, intravenously, 3–4 days before study) to inactivate G_i blocked the effects of UK-14,304. Western blot analysis of receptor expression in whole kidney and preglomerular microvessels revealed similar levels of expression of AT₁, V_1a, and α_2A receptors in SHRs compared with WKY rats. We conclude that activation of α₂-adrenoceptors selectively enhances renovascular responses to angiotensin II and vasopressin in SHRs via an enhanced cross talk between the G_i signal transduction pathway and signal transduction pathways activated by angiotensin II and vasopressin.