The resistance to the natriuretic effect of D1 agonists in spontaneously hypertensive rats is not mediated by increased renal nerve activity, pointing instead to a D1 receptor defect.
D1 natriuresis resistance in SHR models is receptor-intrinsic, not nerve-mediated; leaves open receptor-targeted approaches in human salt-sensitive hypertension.
The resistance of the spontaneously hypertensive rat (SHR) kidney to the natriuretic effect of dopamine and D1 agonists may be due to increased renal nerve activity. Therefore, we compared the effects of the intrarenal arterial infusion of the D1 agonist, SKF 38383, into the denervated (DNX) kidney of saline-loaded-anesthetized SHR and its control, the Wistar-Kyoto (WKY) rat. In both WKY and SHR, DNX of the left kidney slightly decreased urine flow (UV) and absolute (UNaV) and fractional sodium excretion (FENa) in the innervated right kidney; neither vehicle nor D1 agonist infusion exerted any effect. In the left kidney, denervation increased UV, UNaV, and FENa to a similar degree in WKY and SHR (2-fold), without affecting renal blood flow, glomerular filtration rate, or blood pressure. In WKY but not in SHR, after DNX, the D1 agonist dose-dependently increased UV, UNaV, and FENa in the denervated kidney. We conclude that the decreased natriuretic effect of D1 agonists in the SHR is not due to increased renal nerve activity. These data support our previous studies implicating a defect of the D1 receptor or its regulation in the kidney in genetic hypertension.
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Asico et al. (1998) studied this question.
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