Renal and systemic hemodynamic responses to intravenous infusion of leukotriene C4 in the rat.
We studied the systemic and renal hemodynamic effects of leukotriene C4 (2 micrograms/kg per min for 5 minutes, iv) in the rat. During the period of its infusion, leukotriene C4 produced a significant elevation of mean arterial pressure and reductions in cardiac output and renal blood flow, as measured by electromagnetic flow probes. These effects were abolished by FPL55712 , a putative antagonist of sulfidopeptide leukotrienes, but not by saralasin or indomethacin. Leukotriene C4 also resulted in an average loss of 20% in plasma volume which, during the postinfusion period, perpetuated the low cardiac output state and thus provoked the release of angiotensin II. This vasoactive peptide sustained the elevation in systemic vascular resistance and the reduction in renal blood flow over a 70-minute postinfusion observation period. Consequently, glomerular filtration rate fell by approximately 50%. These angiotensin II-mediated effects were abolished by saralasin. Indomethacin prevented the leukotriene C4-induced loss of plasma volume and, thus, allowed for the significant recovery of cardiac output and renal blood flow during the post-infusion period, thereby preserving glomerular filtration rate. We conclude that leukotriene C4 exerts direct systemic and renal vasoconstrictor, as well as cardiodepressant effects, during the period of its infusion. By virtue of its vasopermeability enhancing effect, leukotriene C4 also results in an immediate loss of plasma volume, an effect which requires the presence of secondarily generated cyclooxygenase products and which perpetuates the hemodynamic abnormalities observed beyond the period of leukotriene C4 infusion.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004911:Erythrocyte Volume / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects*; D007263:Infusions, Parenteral; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D013189:SRS-A / Q000008:administration & dosage* / Q000494:pharmacology
D013189:SRS-A