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 co mpare 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 eff ect 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 corres pondingly 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 how 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 a nd 1.0 mg kg(-1) had no effect on basal levels of blood pressure, renal vas cular resistance or renal blood flow. The lower dose of FR139317 had no eff ect 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 mu g kg(-1) min(-1) increased blood pressure by ap proximately 15%, increased renal vascular resistance and decreased renal bl ood 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 bl ood how induced by sarafotoxin 6c was raised (P < 0.01) from 56% to approxi mately 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 how are mediated via ETB rather than ETA receptors. Moreover, both ET-1 and ET-3 dependent vasoconstrictio ns are slightly attenuated by concomitant NO production. By contrast, saraf otoxin 6c appears much more potent at the renal resistance vasculature and is much more powerfully modulated by NO.