Heterogeneity of Vascular Smooth Muscle Responsiveness to Lipid Vasoactive Mediators

Abstract

Thromboxane A₂ (TxA₂), leukotriene C₄ (LTC4), leukotriene D₄ (LTD₄), and platelet-activating factor (PAF) are novel lipids which exert a variety of biological actions. TxA₂, LTC₄ and LTD₄ have been shown to induce direct vasoconstriction in several species, while PAF contracts isolated guinea pig ileum and lung parenchyma. We studied the direct vasoconstricting activities of these lipid mediators in isolated cat renal, superior mesenteric and coronary arteries. The TxA₂ analog 9, 11-methanoepoxy PGH₂ (U-46619) constricted both perfused and helical strips, with the renal and mesenteric arteries being 4 times more responsive than the coronary arteries. LTC4 and LTD₄ constricted coronary arteries to a significantly greater extent than renal and superior mesenteric arteries in both perfused arteries and helical strips. Furthermore, PAF failed to contract any of the perfused arteries or helical strips at concentrations from 1 ng to 20 µg. TxA₂ was a potent vasoconstrictor in all the vessels studied, suggesting a role for this substance as a vasoactive mediator in ischemia and shock. The coronary arteries were more responsive to the leukotrienes than the mesenteric and renal arteries, suggesting that the leukotrienes may play an important role in myocardial ischemia. Moreover, both thromboxane and leukotriene effects were blocked in all preparations by specific receptor antagonists. While the biological effects of PAF are still poorly understood, PAF does not directly vasoconstrict large arteries of the feline renal, superior mesenteric or coronary vasculatures.