Endothelin B receptor antagonism in the rat renal medulla reduces urine flow rate and sodium excretion.
It is well established that activation of endothelin B (ETB) receptor induces natriuresis and diuresis and thus reduces blood pressure. However, the site of action of ETB receptor is debatable. The present study was undertaken to address the role of renal medullary ETB receptor in renal excretory function. In volume-expanded Sprague-Dawley rats, infusion of the ETB antagonist A192621 at 0.5 mg/kg/hr to the renal medulla induced an immediate and significant reduction of urine flow rate that was 87.5% +/- 7.1%, 68% +/- 20%, and 58.3% +/- 15.5% of the control value at 10, 30, and 60 mins, respectively (n=5, P < 0.05 at each time point). Following intramedullary infusion of A192621, urinary sodium excretion remained unchanged during the first 20 mins but started to decline thereafter with a maximal effect at 60 mins. Changes in urinary excretion of potassium and chloride followed the same pattern of changes as for urinary sodium. In contrast, urinary osmolality gradually and significantly increased (control: 419 +/- 66; A192621 at 60 mins: 637 +/- 204 mOsm/kg H2O, P < 0.05). Over a 60-min period of intramedullary infusion of A192621, none of the hemodynamic parameters examined, including mean arterial pressure, renal blood flow, or medullary blood flow, were affected. These data suggest that: (i) intramedullary blockade of ETB receptor produces antidiuresis and antinatriuresis independently of hemodynamic changes, and (ii) the immediate response to intramedullary blockade of ETB receptor is the reduction of water excretion followed by the reduction of sodium excretion.
Guo
Xiaohua
X
Division of Nephrology, University of Utah School of Medicine and Salt Lake Veterans Medical Center, 84148, USA.
Yang
Tianxin
T
D000818:Animals; D004231:Diuresis / Q000187:drug effects*; D065131:Endothelin B Receptor Antagonists; D007262:Infusions, Intravenous; D007679:Kidney Medulla / Q000502:physiology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
C120508:A 192621; D065131:Endothelin B Receptor Antagonists; D011759:Pyrrolidines