Eicosapentaenoic acid-induced endothelium-dependent and -independent relaxation of sheep pulmonary artery

• Published in: European journal of pharmacology Vol. 636; no. 1; pp. 108 - 113
• Main Authors: Singh, Thakur Uttam, Kathirvel, Kandasamy, Choudhury, Soumen, Garg, Satish Kumar, Mishra, Santosh Kumar
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.06.2010; Elsevier
• Subjects: 1400W; Acetylcholine - pharmacology; Animals; Biological and medical sciences; Calcium - metabolism; Calcium Chloride - pharmacology; Eicosapentaenoic acid; Eicosapentaenoic Acid - pharmacology; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Extracellular Space - drug effects; Extracellular Space - metabolism; Fatty Acids - pharmacology; In Vitro Techniques; Intracellular Space - drug effects; Intracellular Space - metabolism; Male; Medical sciences; Nifedipine - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitrites - metabolism; Pharmacology. Drug treatments; Potassium - pharmacology; Pulmonary artery; Pulmonary Artery - drug effects; Pulmonary Artery - metabolism; Pulmonary Artery - physiology; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Sheep; Vasoconstrictor Agents - pharmacology; Vasodilation - drug effects; Eicosapentaenoic acid; Nitric oxide; Pulmonary artery; 1400W; Endothelium; n-3 fatty acid; Vertebrata; Mammalia; Pulmonary vessel; Blood vessel; Animal; Sheep; Circulatory system; Artiodactyla; Ungulata
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.02.041

It is known that long chain polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), have beneficial effects on cardiovascular function including pulmonary hypertension. The purpose of the present study was to examine the mechanisms involved in EPA-induced relaxation of sheep isolated pulmonary artery by measuring isometric tension. Nitric oxide (NO) derived from constitutive nitric oxide synthase (cNOS) was measured by Greiss method in the presence of the inducible nitric oxide synthase (iNOS) selective inhibitor N-[[3-(aminomethyl) phenyl]methyl]-ethanimidamide, dihydrochloride (1400W). EPA (10 − 7–10 − 4 M) caused concentration-dependent relaxation of sheep pulmonary artery with a pD 2 of 5.56 ± 0.09 and E max of 87.40 ± 3.10% ( n = 9). N G -nitro- l-arginine methyl ester (L-NAME) 100 µM significantly attenuated ( E max 41.95 ± 6.70%; n = 8) EPA-induced relaxation of endothelium intact arterial rings. Similarly, endothelium denudation markedly inhibited ( E max 17.60 ± 1.21%; n = 4) EPA-induced relaxation. EPA (30 µM) significantly increased the cNOS-derived NO release (10.17 ± 0.96; n = 8 versus control 7.43 ± 0.78 pmol/mg tissue wet wt./h; n = 7) in endothelium intact vessels. However, EPA-stimulated NO release was markedly blunted by either 100 µM L-NAME (7.07 ± 0.54 pmol/mg tissue wet wt./h; n = 8) or endothelium removal (6.97 ± 0.87 pmol/mg tissue wet wt./h; n = 17). In endothelium-denuded K + (80 mM)-depolarized arterial rings, EPA (30 µM) significantly inhibited CaCl 2-induced contractions ( E max 42.77 ± 5.90% versus control 94.78 ± 9.82%; n = 5). The fatty acid also inhibited nifedipine (1 µM)-insensitive 5-HT-induced contractions in this vessel ( E max 70.57 ± 4.88% versus control 161.50 ± 17.46%; n = 5). In conclusion, EPA relaxes sheep pulmonary artery primarily through endothelium-dependent NO release, and the residual endothelium-independent relaxation may result from inhibition of Ca 2+-influx through L-type calcium channels, as well as 5-HT-stimulated intracellular Ca 2+ release.