The spontaneously hypertensive rat (SHR) is resistant to the paracrine action of renal dopamine. Although the resistance of the SHR to the natriuretic effect of dopamine and its analogues is in part due to an uncoupling of a D1-like receptor from its G-protein/effector enzyme complex in renal proximal tubules, other mechanisms may be involved. Humoral/hormonal factors (e.g. angiotensin II, norepinephrine[NE]) which increase renal sodium transport may also act to oppose the natriuretic effect of dopamine. Since excess NE via increased renal nerve activity in the SHR may act to limit the natriuretic effect of dopamine, we compared the effects of the selective intrarenal arterial infusion of the D1 agonist, SKF 38383, into the chemosurgically denervated (DNX) left kidney in saline-loaded (5% of body weight)-anesthetized SHR (systolic pressure = 218 mm Hg) and its normotensive control, the Wistar-Kyoto (WKY) rat (systolic pressure = 120 mm Hg). Vehicle infusion into the left DNX kidney had no effect on any renal functional parameter. In the right innervated kidney, DNX of the left kidney slightly decreased V and UNaV; neither vehicle nor D1-agonist infusion exerted any effect. However, renal DNX in the left kidney increased urine flow (V) and sodium excretion (UNaV) to a similar degree in WKY and SHR (2-fold, n=5-7/ group), without affecting renal blood flow, glomerular filtration rate, or blood pressure. In WKY, after DNX, the D1 agonist (but not the vehicle), dose-dependently (1.2, 12, and 120 ng/min) increased V (from 13.56 ± 1.83 after DNX to 15.42 ± 1.67, 17.23 ± 2.60, and 19.70 ± 2.98 μl/min, respectively; P≤0.05 120 ng vs DNX, ANOVA, Scheffe's test) and UNaV (from 1.54 ± 0.23 after DNX to 1.98 ± 0.26, 2.53 ± 0.51, 3.08 ± 0.63μEq/min, respectively; P≤0.05 120 ng vs DNX, ANOVA, Scheffe's test). Stopping the agonist resulted in partial recovery of V and UNaV to baseline DNX values. In contrast, in the SHR, the D1 agonist had no effect on any functional parameter after DNX, similar to its inaction in the innervated kidney of the SHR (Hypertension 15: 560, 1990). 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 in the D1 receptor or its regulation in the kidney in genetic hypertension.
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Asico, L., Eisner, G. & Jose, P. RENAL NERVES AND RESISTANCE TO DOPAMINE-D1-MEDIATED NATRIURESIS IN THE SPONTANEOUSLY HYPERTENSIVE RAT † 1634. Pediatr Res 41, 275 (1997). https://doi.org/10.1203/00006450-199704001-01653