Role of endothelin receptor subtypes in the in vivo regulation of renal function

Abstract

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial origin, which at low doses results in renal vasoconstriction and diuresis with variable actions on sodium excretion. The current study conducted in four groups of anesthetized dogs was designed to define the role of the ETA and ETB receptor subtypes in the renal actions of low-dose exogenous ET. Group 1 (n = 4) animals served as time controls. In group 2 (n = 6) a systemic ET-1 (5 ng.kg-1.min-1) infusion mediated renal vasoconstriction, antinatriuresis with increases in proximal fractional reabsorption of sodium, and diuresis with a decrease in urine osmolality. In group 3 (n = 6) intrarenal BQ-123 (4 micrograms.kg-1.min-1), a selective ETA antagonist, abolished the systemic ET-1-mediated changes in renal hemodynamics and unmasked a natriuretic action at the level of the proximal tubule. In contrast, the diuretic response of ET was not altered by BQ-123. In group 4 (n = 6) intrarenal sarafotoxin 6-c, a selective ETB receptor agonist, resulted in a diuretic response without a change in sodium excretion. These studies suggest that the ETA receptor contributes to the renal vasoconstriction, whereas the ETB receptor is largely responsible for the diuretic response during exogenous ET. This study also suggests that at low doses ET is natriuretic in vivo by decreasing proximal tubular reabsorption of sodium independent of ETA or ETB receptor activation.

Endothelin-A Blockade Attenuates Systemic and Renal Hemodynamic Effects of L-NAME in Humans

“…A similar vasodilatory action of ET A blockade was found in dog kidney, with a substantial increase in RBF in the absence of significant changes in MAP. 12 In addition, ET A blocking agents, even at doses devoid of systemic and renal vasodilatory effects, largely prevented renal vasoconstriction due to systemic infusion of ET-1 in conscious dog 17 and in humans. 13 Finally, infusion of the selective ET B receptor agonist ET3 did not affect kidney function of healthy humans.…”

“…It is generally believed that Na retention produced by infusion of ET-1 in both animals and humans results merely from renal vasoconstriction secondary to ET A receptor activation. 17,18 Because low doses of ET-1 may be natriuretic in animals via activation of ET B receptors, 6,7 it is conceivable that ET A receptor blockade unmasks an ET B -dependent natriuresis. However, BQ-123 did not affect either baseline Li or Na excretion or their increased reabsorption during L-NAME infusion.…”

Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems

“…Interestingly, in vivo studies revealed that administration of ET-1 resulted in reduced renal hemodynamics and kidney dysfunction, similar to those found during pneumoperitoneum (9). For instance, whole organ studies in intact rats have demonstrated that a shortlasting infusion of ET-1 into the renal artery decreases renal plasma flow (RPF), GFR, and urine volume (5,22,38,46). Similarly, a long-term infusion of ET-1 into conscious dogs results in increased renal vascular resistance and decreased GFR and RPF (5,46).…”

“…For instance, whole organ studies in intact rats have demonstrated that a shortlasting infusion of ET-1 into the renal artery decreases renal plasma flow (RPF), GFR, and urine volume (5,22,38,46). Similarly, a long-term infusion of ET-1 into conscious dogs results in increased renal vascular resistance and decreased GFR and RPF (5,46). Hence, it is proposed that activation of the ET system may be involved in pneumoperitoneum-induced renal dysfunction.…”

Renal endothelin in heart failure and its relation to sodium excretion

“…8 The sodium retentive activity of circulating ET-1 in human beings was demonstrated by low-dose infusion of exogenous ET-1 (1 ng/kg per minute), which caused sodium retention without any changes in renal plasma flow. 24 ET-1 locally produced in the kidney also seems to participate in sodium and water handling, favoring sodium retention and increasing free water clearance.…”