Effects of Endothelin on Blood Pressure and Renal Hemodynamics in Doca-Salt Hypertensive Rats Under Conscious and Unrestrained Condition

The acute effects of endothelin, a potent vasoconstrictor peptide, were investigated on renal hemodynamics, blood pressure and heart rate in conscious and unrestrained DOCA-salt hypertensive rats to compare with those in normotensive, sham-operated rats. The plasma concentration of immunoreactive endothelin was measured following the administration of endothelin, 0.4 nmole IV. After a dose of 1 nmole/kg IV, the blood pressure fell transiently and then rose gradually, while the renal blood flow remained decreased throughout the observation period. Both the blood pressure elevation and the renal blood flow decline in DOCA-salt hypertensive rats exceeded that in controls. In both experimental groups the arterial plasma endothelin concentration decreased rapidly after the peak was achieved. The disappearance of endothelin from plasma was significantly delayed in the DOCA-salt hypertensive rats. These findings suggest that the marked increase in blood pressure and the altered renal hemodynamics induced by endothelin in DOCA-salt hypertensive rats are due in part to a decrease in endothelin clearance.