Actions of endogenous endothelin on glomerular hemodynamics in the rat

Both endothelin (ET) ETA/ETB receptors are distributed in the glomerular microcirculation, but their physiological functions, if any, are unknown. We used a nonpeptide mixed ETA/ETB receptor antagonist (Bosentan) and a selective ETA receptor antagonist (BQ-123) to investigate the glomerular hemodynamic actions of endogenous ET in the anesthetized euvolemic rat. Blockade of ETA and ETB receptors with Bosentan produced a small fall in systemic blood pressure and a large fall in glomerular blood pressure due to a significant increase in preglomerular (afferent) arteriolar resistance. Single-nephron glomerular filtration rate was not reduced because of an offsetting rise in the glomerular capillary ultrafiltration coefficient. Blockade of the selective ETA receptor with BQ-123 had no effect on blood pressure or glomerular hemodynamics. These observations indicate that endogenous ET is of physiological importance in control of glomerular hemodynamics. Surprisingly, endogenous ET tonically dilates rather than contracts the preglomerular arteriole, and it also tonically lowers the glomerular capillary ultrafiltration coefficient, probably by contracting the mesangial cell. All physiological glomerular actions of ET are mediated via the ETB receptor.