title: Influence of endothelins and sarafotoxin 6c and L-NAME on renal vasoconstriction in the anaesthetized rat.
abstract: 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.
authors.affiliation: Department of Physiology, The Medical School, Birmingham B15 2TT.
authors.forename: J L
authors.initials: JL
authors.lastname: Marshall
authors.forename: E J
authors.initials: EJ
authors.lastname: Johns
mesh_terms: D000758:Anesthesia; D000818:Animals; D016232:Endothelins / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014757:Viper Venoms / Q000494:pharmacology*
chemical_list: D016232:Endothelins; D014757:Viper Venoms; C057354:sarafotoxins s6; D019331:NG-Nitroarginine Methyl Ester