Influence of endothelins and sarafotoxin 6c and L-NAME on renal vasoconstriction in the anaesthetized rat.

1. An investigation was performed in pentobarbitone anaesthetized rats to compare the renal vasoconstrictor actions of endothelin-1 (ET-1), endothelin-3 (ET-3) and sarafotoxin 6c and their dependency on NO production. 2. Intra-renal arterial infusion of ET-1 and ET-3, from 1 - 1000 ng had no effect on blood pressure, but reduced renal blood flow maximally by 82 and 81% with EC50 values of 510+/-18 and 1113+/-17 ng, respectively and correspondingly increased renal vascular resistance and decreased conductance. 3. Direct renal arterial administration of sarafotoxin 6c was without effect on blood pressure but caused a maximum reduction in renal blood flow of 56% at 300 ng and had an EC50 of 86+/-4 ng. 4. Administration of the selective ETA receptor antagonist FR139317 at 0.3 and 1.0 mg kg-1 had no effect on basal levels of blood pressure, renal vascular resistance or renal blood flow. The lower dose of FR139317 had no effect on the ET-1 dose-response curve for renal blood flow while at 1.0 mg kg-1, FR139317 reduced the EC50 to 363+/-32 ng (P<0.05). 5. Infusion of L-NAME, 10 microg kg-1 min-1 increased blood pressure by approximately 15%, increased renal vascular resistance and decreased renal blood flow by some 40%. The EC50 values for renal blood flow were reduced to 358+/-68 ng (P<0.05) for ET-1, 638+/-69 ng (P<0.05) for ET-3 and 55+/-10 ng (P<0.01) for sarafotoxin 6c. The maximal reduction in renal blood flow induced by sarafotoxin 6c was raised (P<0.01) from 56% to approximately 100% and renal vascular resistance increased when NO production was blocked. 6. These results showed that the vasoconstrictor actions of ET-1 and ET-3 on resistance vessels controlling renal blood flow are mediated via ETB rather than ETA receptors. Moreover, both ET-1 and ET-3 dependent vasoconstrictions are slightly attenuated by concomitant NO production. By contrast, sarafotoxin 6c appears much more potent at the renal resistance vasculature and is much more powerfully modulated by NO.