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

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. 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. 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. 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