In vivo effects of leukotriene B4, C4 and D4. Evidence that changes in blood pressure are mediated by prostaglandins

Abstract

Intra-jugular nanomole injections of leukotrienes B₄, C₄ and D₄ (LTB₄, LTC₄, LTD₄) in anesthetized guinea-pigs have been shown to cause dose-dependent increases of the mean arterial blood pressure. While the responses to LTB₄ were monophasic, the responses to LTC₄ and LTD₄ were characterized by a fast (10–50 sec), medium high, first pressor phase followed by a second, longer lasting (3–9 min), more important pressor phase. Like antigen-antibody reactions, leukotrienes induced cardiac effects such as tachycardia and rhythm disturbances as well as respiratory difficulties, convulsions and sometimes death of the animals. The prostaglandin synthesis inhibitor, indomethacin, reduced the pressor response and the tachyarrhythmic effects of LTB₄, C₄ and D₄. These results raise the possibility that leukotrienes produce their hemodynamic effects in guinea-pigs by stimulating the synthesis and release of biologically active derivatives of arachidonic acid.