Renal vascular effects of leukotriene C4 in the isolated perfused kidney of the rat.
1 The vascular effects of leukotriene C4 (LTC4) were investigated in the isolated perfused kidney of the rat. 2 LTC4 (6.4 X 10(-10) to 3.2 X 10(-8) mol kg-1 min-1 given over 5 min) resulted in a prompt, dose-dependent increase in renal vascular resistance in a recirculating system, which lasted for more than 60 min. 3 LTC4 was 10 to 20 fold and 1000 to 2000 fold, respectively, less active on a molar basis than noradrenaline and angiotensin II in eliciting renal vasoconstriction. 4 The vascular response to LTC4 was blocked dose-dependently by FPL 55712, an antagonist of slow reacting substance of anaphylaxis. OKY 1581, a specific thromboxane synthetase inhibitor, and indomethacin, a cyclo-oxygenase inhibitor, did not influence the LTC4 response. 5 LTC4 given in a single-pass perfusion system resulted in a short lasting response with baseline values for renal vascular resistance reached after 4 min. 6 These results show that LTC4 is a short acting renal vasoconstrictor with less potency than noradrenaline and angiotensin II. Its pressor effects seem to be mediated by specific leukotriene receptors and independent of cyclo-oxygenase products. The long-lasting effect in the recirculating arrangement, in contrast to the single pass system, is compatible with formation of active metabolite(s).
Frölich
J C
JC
Department of Clinical Pharmacology, Hannover Medical School, Germany.
Yoshizawa
M
M
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D002867:Chromones; D013189:SRS-A; D000804:Angiotensin II; C006312:FPL 55712; D009638:Norepinephrine; D007213:Indomethacin