Vasodilator Action of Docosahexaenoic Acid (DHA) in Human Coronary Arteries In Vitro

Kuen-Tze Wu；Ching-Ting Huang；Jeng Wei；Lih-Min Tsai；Chih-Hsueng Hsu；Yao-Chang Chen；Jung-Mou Yang；Cheng-I Lin

docosahexaenoic acid DHA ； explanted human hearts ； coronary artery smooth muscle ； rapid A-type K(superscript +) currents ； inwardly rectifying K(superscript +) currents I(subscript K1) ； voltage-gated K(super

The Chinese Journal of Physiology

50卷4期（2007 / 08 / 31）

164 - 170

英文

Coronary arterial tissues obtained from mammalian hearts are known to develop spontaneous phasic contractions. The aim of the present study was to investigate the vasodilatory effects of docosahexaenoic acid (DHA) on the rhythmic contractions of isolated human coronary arterial (HCA) preparations obtained from the recipient hearts of patients undergoing cardiac transplantation. Results from 8 hearts show that: (i) most HCA tissues displayed spontaneous rhythmic phasic contractions with a cycle length around 10min in the absence or presence of PGF(subscript 2α) or elevated [K(superscript +)](subscript o) (20mM); (ii) the rhythmic activity could be suppressed by a free fatty acid DHA (30μM); (iii) high [K(superscript +)](subscript o) (20 and 80mM) could induce sustained tonic contraction in addition to phasic contractions in HCA tissues, the tonic contraction could be antagonized by L-type Ca(superscript 2+) channel blockers or by DHA (depending on [K(superscript +)](superscript o)); (iv) a digitalis substance ouabain also could induce tonic contraction and suppress phasic contraction; (v) in isolated HCA vascular smooth muscle cells, DHA increased the magnitude of outward voltagegated K(superscript +) (I(subscript KV)) currents and the inwardly rectifying I(subscript K1) currents. Enhancement of K(superscript +) currents could be related to vasorelaxation induced by DHA in HCA preparations. Further studies on the effects of DHA on various ionic currents and intracellular Ca(superscript 2+) transient are needed to clarify the Ca(superscript 2+)-dependent and the Ca(superscript 2+)-independent actions of DHA in HCA.

1. Amberg, G.C.,Koh, S.D.,Imaizumi, Y.,Sanders, K.M.(2003).A-type potassium currents in smooth muscle.Am. J. Physiol. (Cell Physiol.),284,583-595.
2. Asano, M.,Nakajima, T.,Iwasawa, K.,Asakura, Y.,Morita, T.,Nakamura, F.,Tomaru, T.,Wang, Y.,Goto, A.,Toyo-oka, T.,Soma, M.,Suzuki, S.,Okuda, Y.(1999).Eicosapentaenoic acid inhibits vasopressin-activated Ca《sup》2+《/sup》 influx and cell proliferation in rat aortic smooth muscle cell lines.Eur. J. Pharmacol.,379,199-209.
3. Dagassan, P.H.,Clozel, M.,Breu, V.,Clozel, J.P.(1995).Role of endothelin in spontaneous phasic contraction of human coronary arteries.J. Cardiovasc. Pharmacol,26,200-203.
4. Engler, M.B.,Engler, M.M.(2000).Docosahexaenoic acid-induced vasorelaxation in hypertensive rats: mechanisms of action.Biol. Res. Nurs.,2,85-95.
5. Gollasch, M.,Ried, C.,Bychkov, R.,Luft, F.C.,Haller, H.(1996).K《sup》+《/sup》currents in human coronary artery vascular smooth muscle cells.Circ. Res.,78,676-688.
6. Jackson, W.F.(2000).Ion channels and vascular tone.Hypertension,35,173-178.
7. Kalsner, S.(1997).Vasodilator action of calcium antagonists in coronary arteries in vitro.J. Pharmacol. Exp. Ther.,281,634-642.
8. Lin, C.I.,Wu, S.L.,Tao, P.L.,Chen, H.M.,Wei, J.(1993).The role of cyclic AMP and phosphodiesterase activity in the mechanism of action of tetramethylpyrazine on human and dog cardiac and dog coronary arterial tissues.J. Pharm. Pharmacol.,45,963-966.
9. Ross, R.(1971).The smooth muscle. II. Growth of smooth muscle in culture and formation of elastic fibers.J. Cell Biol.,50,172-186.
10. Sabouni, M.H.,Mustafa, S.J.(1989).Effects of adenosine analogs and ouabain on rhythmicity in human coronary artery.Eur. J. Pharmacol.,168,271-276.
11. Schror, K.(1993).The effect of prostaglandins and thromboxane A2 on coronary vessel tone-mechanisms of action and therapeutic implication.Eur. Heart J.,14,34-41.
12. Tosun, M.,Paul, R.J.,Rapoport, R.M.(1997).Intracellular Ca《sup》2+《/sup》 elevation and contraction due to prostaglandin F2α in rat aorta.Eur. J. Pharmacol.,340,203-208.
13. Vassalle, M.,Lin, C.I.(2004).Calcium overload and cardiac function.J. Biomed. Sci.,11,542-565.
14. Xu, X.,Rials, S.J.,Wu, Y.,Marinchak, R.A.,Kowey, P.R.(1999).The properties of the inward rectifier potassium currents in rabbit coronary arterial smooth muscle cells.Pflugers Arch.-Eur. J. Physiol.,438,187-194.
15. Zaritsky, J.J.,Eckman, D.M.,Wellman, G.C.,Nelson, M.T.,Schwarz, T.L.(2000).Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K《sup》+《/sup》 current in K《sup》+《/sup》-mediated vasodilation.Circ. Res.,87,160-166.

1. Tsai, Yi-Ting,Tsai, Chien-Sung,Loh, Shih-Hurng,Lee, Chung-Yi,Cheng, Tzu-Hurng,Chang, Yi-Yu,Chang, Chung-Yi(2014).Functional Characterization of Intracellular pH Regulators Responsible for Acid Extrusion in Human Radial Artery Smooth Muscle Cells.中國生理學雜誌,57(5),238-248.