Endothelin-specific antibodies decrease blood pressure and increase glomerular filtration rate and renal plasma flow in spontaneously hypertensive rats

OBJECTIVEStudies were undertaken to clarify the pathophysiologic significance of endogenous endothelin in the control of blood pressure and renal hemodynamics in spontaneously hypertensive rats (SHR). DESIGNThe technique of passive immunization was used to neutralize endogenous endothelin in order to estimate the contribution of endothelin to the in vivo control of blood pressure and renal hemodynamics. METHODSEndothelin-specific antibodies were administered intravenously into anesthetized SHR and Wistar-Kyoto (WKY) rats, and the effects upon blood pressure and renal function (renal plasma flow and glomerular filtration rate) assessed. Using the same antibodies, baseline plasma levels of endothelin in both strains of rats were determined by radioimmunoassay. RESULTSInfusion of endothelin-specific antibodies into SHR decreased mean arterial pressure by approximately 10% and renal vascular resistance and renal vascular resistance by approximately 35%. Glomerular filtration rate and renal plasma flow both increased by approximately 50% over control. In contrast, infusion of normal rabbit serum into SHR or of endothelin-specific antibodies into WKY rats did not result in any significant change in renal hemodynamics or arterial blood pressure. Baseline plasma levels of immunoreactive endothelin in SHR were significantly lower than those in WKY rats. CONCLUSIONThese results suggest that endothelin plays an important role in the modulation of systemic blood pressure and renal function in SHR.