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ET_A receptor blockade prevents renal dysfunction in salt-sensitive hypertension induced by sensory denervation

Departments of ¹Medicine and ²Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan

Submitted 15 April 2005 ; accepted in final form 21 June 2005

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 sc) 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·kg^–1·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·min^–1·100 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.

blood pressure; capsaicin; endothelin receptor; kidney

This article has been cited by other articles:

				Y. Wang, A. F. Chen, and D. H. Wang Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H3136 - H3143. [Abstract] [Full Text] [PDF]