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(Hypertension. 1998;31:615-620.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Linoleic Acid Induces Relaxation and Hyperpolarization of the Pig Coronary Artery

Silvia I. Pomposiello; Magaly Alva; Dixon W. Wilde; ; Oscar A. Carretero

From the Hypertension and Vascular Research Division, Department of Medicine, Heart and Vascular Institute, Henry Ford Hospital, Detroit (S.I.P., M.A., O.A.C.), and the Department of Anesthesiology, University of Michigan, Ann Arbor (D.W.W.), Mich.

Correspondence to Oscar A. Carretero, MD, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202.

Abstract—Linoleic acid, a polyunsaturated C₁₈ fatty acid, is one of the major fatty acids in the coronary arterial wall. Although diets rich in linoleic acid reduce blood pressure and prevent coronary artery disease in both humans and animals, very little is known about its mechanism of action. We believed that its beneficial effects might be mediated by changes in vascular tone. We investigated whether linoleic acid induces relaxation of porcine coronary artery rings and the mechanism involved in this process. Linoleic acid and two of its metabolites, 13-hydroxyoctadecadienoic acid (13-HODE) and 13-hydroperoxyoctadecadienoic acid (13-HPODE), induced dose-dependent relaxation of prostaglandin (PG) F₂–precontracted rings that was not affected by indomethacin (10^-5 mol/L), a cyclooxygenase inhibitor, or cinnamyl-3,4-dihydroxy--cyanocinnamate (CDC; 10^-5 mol/L), a lipoxygenase inhibitor. Removal of endothelial cells had no effect on vasorelaxation, suggesting a direct effect on the vascular smooth muscle cells (VSMC). When rings were contracted with KCl, linoleic acid failed to induce relaxation. Although tetrabutylammonium (5x10^-3 mol/L), a nonselective K⁺ channel blocker, slightly inhibited the relaxation caused by linoleic acid, glibenclamide (10^-6 mol/L), an ATP-sensitive K⁺ channel blocker, and charybdotoxin (7.5x10^-8 mol/L) or tetraethylammonium (5x10^-3 mol/L), two different Ca²⁺-activated K⁺ channel blockers, had no effect. However, relaxation was completely blocked by ouabain (5x10^-7 mol/L), a Na⁺/K⁺-ATPase inhibitor, or by a K⁺-free solution. In addition, linoleic acid (10^-6 mol/L) caused sustained hyperpolarization of porcine coronary VSMC (from -49.5±2.0 to -60.7±4.2 mV), which was also abolished by ouabain. We concluded that linoleic acid induces relaxation and hyperpolarization of porcine coronary VSMC via a mechanism that involves activation of the Na⁺/K⁺-ATPase pump.

Key Words: linoleic acid • nitric oxide • prostaglandins • endothelium-derived hyperpolarizing factor • cyclooxygenase • Na⁺/K⁺-ATPase inhibitor

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