High salt intake increases endothelin B receptor function in the renal medulla of rats

Abstract

Aims: Endothelin (ET)-1 promotes natriuresis via the endothelin B receptor (ETB) within the renal medulla. In male rats, direct interstitial infusion of ET-1 into the renal medulla has no effect on renal sodium and water excretion but is associated with endothelin A receptor (ETA)-dependent reductions in medullary blood flow. Loss of ETB function leads to salt-sensitive hypertension. We hypothesized that HS intake would increase the natriuretic and diuretic response to renal medullary infusion of ET peptides.

Main methods: Male Sprague-Dawley (SD) rats were fed a normal (NS) or high (HS) salt diet for 7days. Rats were anesthetized and a catheter implanted in the renal medulla for interstitial infusion along with a ureteral catheter for urine collection. Medullary infusion of a low dose of ETB receptor agonist, sarafotoxin 6c (S6c; 0.15μg/kg/h), or ET-1 (0.45μg/kg/h) was used to determine changes in sodium excretion (UNaV).

Key findings: In HS fed rats, intramedullary infusion of a low dose of S6c induced a significant increase in UNaV, roughly 2-fold over baseline, compared to no response to this low dose in NS fed rats. In HS fed rats, intramedullary infusion of ET-1 induced a significantly greater increase in UNaV compared to NS fed rats, although this increase was not different from the HS time control studies.

Significance: We conclude that high salt intake enhances the diuretic and natriuretic effects of ETB receptor activation in vivo consistent with a role for the ETB receptor in maintaining fluid-electrolyte homeostasis.

Keywords: Diuresis; Endothelin receptor; High salt; Natriuresis.

Figure 1

Sodium excretion (A, D, G), urine flow (B, E, H) and mean arterial pressure (C, F, I) during a baseline period and the 2^nd experimental period of intramedullary infusion of saline (A–C) or S6c (D–F) or ET-1 (G–I) in anesthetized Sprague-Dawley rats. Black symbols denote high salt (HS) fed rats and white symbols denote normal salt (NS) fed rats. * P < 0.05 vs NS for the same time; ^† P < 0.05 vs baseline period; § P < 0.05 vs HS time control group. n = 8~11 each group.

Figure 2

Saturation binding curves (A) and maximum binding (Bmax) (B) for [¹²⁵I]-ET-1 in plasma membrane preparations from renal inner medullary tissue taken from rats on a normal salt (NS) or high salt (HS) diet; n=6,5 rats, respectively. * P < 0.05 vs NS