Involvement of Renal Nerves and Endothelins in the Regulation of Renal Water Excretion in Diabetes insipidus Rats

Abstract

The interaction between renal nerves, endothelins acting via endothelin-A receptors and vasopressin in the regulation of renal excretory function was investigated. In conscious intact and renal denervated diabetes insipidus (DI) Brattleboro rats, as well as their controls, Long-Evans (LE) rats, an infusion of 16.4 nmol/kg/min ET_A receptor antagonist BQ-123 was performed in the course of 50 min. Femoral artery blood pressure, heart rate, C_cr, V · U_Na, V · U_K and V · U_Cl did not alter in any of the groups. Urine flow rate diminished by 38.1% (p < 0.02), while urine osmolality increased by 30.3% (p < 0.05) as a result of BQ-123 infusion in the intact LE rats but neither urine flow rate nor urine osmolality changed in the DI rats. In contrast to intact LE rats, BQ-123 infusion in renal denervated LE rats did not alter urine flow rate or urine osmolality. However, urine flow rate in renal denervated DI rats surprisingly decreased by 71.1% (p < 0.01) while urine osmolality increased by 161% (p < 0.001) as a result of BQ-123 infusion. Endogenous endothelins can regulate renal water excretion through ET_A receptor activation. Renal sympathetic nerves participate in the modulation of renal water excretion influencing the ET_A receptor-mediated effects of endothelins in the kidney.

Impaired response of the denervated kidney to endothelin receptor blockade in normotensive and spontaneously hypertensive rats

“…Intravenous treatment with the ET B receptor antagonist BQ-788, 25 nmol/kg.min at an infusion rate of 25 lL/min for 50 minutes, was performed in the fifth group of intact rats, six WKY rats and six spontaneously hypertensive rats, and in the sixth group of rats with BRD, six WKY rats and six spontaneously hypertensive rats. Doses of BQ-123 [11] and BQ-788 [12] used in the present study, were previously shown not to affect arterial blood pressure.…”

Renal endothelin system and excretory function in Wistar–Kyoto and Long–Evans rats

“…Continuous infusion of BQ‐123 and BQ‐788 was chosen to provide ET receptor blockade throughout the experimental period and the doses of BQ‐123 and BQ‐788 used in the present study were shown previously to effectively block renal ET receptors but to have no effect on systemic arterial BP (Matsuura et al. 1997, Girchev et al. 2001).…”

“…We have previously observed that ET A receptor blockade with BQ‐123 had no effect on renal electrolyte excretion in Long–Evans (LE) (Girchev et al. 2001) but significantly reduced urinary sodium and potassium excretion in Wistar–Kyoto (WKY) rats (Girchev et al.…”