Divergent influences of leukotrienes C4, D4, and E4 on mesenteric and renal blood flow

Abstract

Influences of leukotrienes C4 (LTC4), D4 (LTD4), and E4 (LTE4) on mesenteric and renal blood flow were investigated in the anesthetized dog. Blood flow was measured with noncannulating electromagnetic flow probes, and all agonists were injected as a bolus close arterially. When injected into the superior mesenteric artery, LTC4 (0.1-3.0 ng), LTD4 (0.1-1.0 ng), and LTE4 (1-30 ng) produced dose-dependent decreases in blood flow in absence of a change in mean arterial pressure. When compared with intestinal vasoconstrictor responses caused by angiotension II, which was most active, and norepinephrine, which was least active, the leukotrienes were intermediate between these two well-known vasoactive hormones. LTD4 was more active than LTC4, and both were considerably more active than LTE4. In contrast to the intestine, injection of leukotrienes (1,000 ng) into the kidney resulted in little to no change in renal blood flow or mean arterial pressure, but mesenteric flow decreased 10-15 s later. Administration of indomethacin (5 mg/kg iv) did not alter mesenteric vasoconstrictor responses produced by LTD4. However, mesenteric vasoconstrictor responses to prostaglandin (PG)D2 were reduced after indomethacin, whereas renal vasodilation caused by PGD2 was unaffected. These results demonstrate that LTC4, LTD4, and LTE4 differentially affect blood flow in the intestine and kidney and suggest that if circulating levels of leukotrienes are increased, blood flow would be expected to be diverted away from the intestine. These data are thus compatible with the hypothesis that leukotrienes may participate in regulation of peripheral regional blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)