Leukotriene cardiovascular effects

Cysteinyl leukotrienes can induce an early, transient fall in arterial pressure associated with sympathoadrenergic activation, plus a late rise in small coronary arteriolar resistance [32]. Using specific antagonists of CysFTi and CysFT2 [63] it will be possible to assess the each receptor s contribution to the cardiovascular effects of these vasoactive mediators. 

Herman, C.A., Charlton, G.A. and Cranfill, R.L. (1991) Metabolism and cardiovascular effects of leukotrienes in warm- and cold-acclimated American bullfrogs (Rana catesheiana). Am. J. Physiol. 260, R834-R838... 

Although they remain less effective than inhaled corticosteroids, a 5-LOX inhibitor (zileuton) and selective antagonists of the CysLTl receptor for leukotrienes (zafirlukast, montelukast, and pranlukast see Chapter 20) are used clinically in mild to moderate asthma. Growing evidence for a role of the leukotrienes in cardiovascular disease has expanded the potential clinical applications of leukotriene modifiers. Conflicting data have been reported in animal studies depending on the disease model used and the molecular target (5-LOX versus FLAP). Human genetic studies have demonstrated a link between cardiovascular disease and polymorphisms in the leukotriene biosynthetic enzymes, in particular FLAP, in some populations. 

Leukotrienes C4 and D4 also have very pronounced effects on the cardiovascular system. They are, for example, very effective coronary artery vasoconstrictors. A number of indirect effects have also been attributed to LTC4 and LTD4. For example, these agents effect the secretion of mucous in the respiratory tract and cause negative inotropic effects in mammalian heart preparations. Many other biological activities have been associated with the peptido-leukotrienes. 

Research has identified differential effects of the n-6 and n-3 families of polyunsaturated fatty acids on plasma hpid profiles, inflammatory response and cardiovascular risk. As the primary substrate for 5-lipoxygenase, n-6 and its metabohe precursor, linoleic acid, enhance the production of leukotrienes, which could induce arterial atherogenesis.35 In addition, variants of the 5-lipoxygenase gene promoter may... 

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