EFFECT OF ENDOTHELIN-1 ON GLOMERULAR HYDRAULIC PRESSURE AND RENIN RELEASE IN DOGS

The present study was designed to analyze quantitatively the effects of a wide range of endothelin-1 levels on renal hemodynamics and renin release in the canine nonfiltering kidney, including their effects on glomerular hydraulic pressure. Intrarenal infusion of endothelin-1 produced dose-dependent reductions in renal blood flow, but it did not affect glomerular hydraulic pressure until the infused dose reached high rates. At the rate of 1.0 ng/kg per minute, endothelin-1 reduced renal blood flow by 23% (p<0.01), whereas glomerular hydraulic pressure was not significantly changed from 68.1 +/- 1.3 to 67.4 +/- 1.2 mm Hg. However, with a higher rate of endothelin-I infusion (5.0 and 10.0 ng/kg per minute), glomerular hydraulic pressure fell to 59.5 +/- 1.3 and 51.5 +/- 1.8 mm Hg (p<0.01), whereas renal blood How was reduced from 154.5 +/- 15 to 83.0 +/- 9.5 and 53.5 +/- 9.9 mL/min, respectively. Endothelin-1 infusion also produced an inhibitory effect on renin release. With infusion at 1.0 ng/kg per minute, renin release fell from the control level of 47.9 +/- 5.6 to 26.6 +/- 4.9 units/min per gram kidney weight (p<0.01), and it fell further to 16.1 +/- 4.3 units/min per gram kidney weight with infusion at 10.0 ng/kg per minute. In summary, endothelin-1 infusion did not affect glomerular hydraulic pressure despite a fall in renal blood flow at low doses, but at high doses it reduced both, suggesting that endothelin-1 exerts separate, dose-dependent effects on preglomerular and postglomerular resistances. In addition, the present study demonstrated that endothelin-1 infusion has an ability to inhibit renin release in vivo when the macula densa-mediated pathway is eliminated.