ROLES OF PROSTAGLANDINS AND NITRIC-OXIDE IN THE EFFECT OF ENDOTHELIN-1 ON RENAL HEMODYNAMICS

It is known that endothelin-1 stimulates the release of nitric oxide a nd prostaglandins in various vascular beds. We designed the present st udy to analyze the roles of prostaglandins and nitric oxide in the eff ect of endothelin-1 on the regulation of renal hemodynamics and renin release, We used N-omega-nitro-L-arginine methyl ester (L-NAME) and me clofenamic acid to inhibit the production of nitric oxide and prostagl andins, respectively. With a nonfiltering kidney model, renal blood fl ow was reduced 21% in dogs treated with L-NAME and 18% in dogs treated with meclofenamic acid. Inhibition of nitric oxide and prostaglandins , however, produced opposite effects on estimated glomerular hydraulic pressure: L-NAME increased glomerular hydraulic pressure from 63.1+/- 0.9 to 64.6+/-1.3 mm Hg (P<.01), and meclofenamic acid reduced glomeru lar hydraulic pressure from 63.3+/-1.4 to 59.8+/-1.6 mm Hg (P<.01). En dothelin-1 infusion produced a dose-dependent reduction in renal blood flow after blockade of nitric oxide and prostaglandins. The responses of glomerular hydraulic pressure were different in the two groups dur ing endothelin-1 infusion. Endothelin-1 progressively reduced glomerul ar hydraulic pressure in a dose-dependent fashion in the meclofenamic acid group. However, endothelin-1 slightly increased glomerular hydrau lic pressure until the infusion rate reached 5.0 ng/kg per minute. At that rate, endothelin-1 reduced glomerular hydraulic pressure from 63. 3+/-1.4 to 47.0+/-1.4 mm Hg in the meclofenamic acid group (P<.01), a more than 25% reduction. whereas at the same dose, endothelin-1 reduce d glomerular hydraulic pressure only less than 2% in the L-NAME group. In addition, blockade of nitric oxide and prostaglandins did not alte r the inhibitory effect of endothelin-1 on renin release in the nonfil tering kidney. Therefore, the present study demonstrates that the rele ase of nitric oxide and prostaglandins might modulate the effects of e ndothelin-1 on the renal circulation. The present findings suggest tha t the differential vasoconstrictive effects of endothelin-1 on preglom erular and postglomerular vessels are associated with its stimulation of nitric oxide and prostaglandin production.