α2-Adrenoceptors Potentiate Angiotensin II- and Vasopressin-Induced Renal Vasoconstriction in Spontaneously Hypertensive Rats

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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 Gi 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 Gi 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 Gi 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, V1a, and α2A 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 Gi signal transduction pathway and signal transduction pathways activated by angiotensin II and vasopressin.