ET(A) receptor blockade prevents renal dysfunction in salt-sensitive hypertension induced by sensory denervation.

To test the hypothesis that activation of the endothelin type A (ET(A)) receptor contributes to decreased renal excretory function and increased blood pressure in sensory nerve-degenerated rats fed a high-salt diet, neonatal Wistar rats were given vehicle or capsaicin (CAP, 50 mg/kg s.c.) on the first and second day of life. After being weaned, vehicle or CAP-treated rats were fed a normal (NS, 0.5%) or a high- (HS, 4%) sodium diet for 2 wk with or without ABT-627 (5 mg x kg(-1) x day(-1), a selective ET(A) receptor antagonist). Systolic blood pressure increased in CAP-treated rats fed a HS diet (CAP-HS) compared with vehicle-treated rats fed a HS diet (CON-HS, 145 +/- 7 vs. 89 +/- 5 mmHg, P < 0.05). Creatinine clearance and fractional sodium excretion (FE(Na)) decreased in CAP-HS rats compared with CON-HS rats (creatinine clearance, 0.54 +/- 0.05 vs. 0.81 +/- 0.09 ml x min(-1) x 100 g body wt(-1); FE(Na), 8.68 +/- 0.99 vs. 12.53 +/- 1.47%, respectively; P < 0.05). Water and sodium balance increased in CAP-HS rats compared with CON-HS (water balance, 20.2 +/- 1.5 vs. 15.5 +/- 1.9 ml/day; sodium balance, 11.9 +/- 3.1 vs. 2.4 +/- 0.3 meq/day, respectively; P < 0.05). The endothelin (ET)-1 levels in plasma and isolated glomeruli increased by about twofold in CAP-HS rats compared with CON-HS rats (P < 0.05). ABT-627 prevented the decrease in creatinine clearance and FE(Na), the increase in water and sodium balance, and the increase in blood pressure in CAP-HS rats (P < 0.05). Therefore, the blockade of the ET(A) receptor ameliorates the impairment of renal excretory function and prevents the elevation in blood pressure in salt-sensitive hypertension induced by degeneration of sensory nerves, indicating that the activation of the ET(A) receptor impairs renal function and contributes to the development of a salt-induced increase in blood pressure in this model.