Chronic hypoxia alters fatty acid composition of phospholipids in right and left ventricular myocardium

Adult male Wistar rats were exposed to intermittent high altitude hypoxia of 7000 m simulated in a hypobaric chamber for 8 h/day, 5 days a week; the total number of exposures was 25. The concentration of individual phospholipids and their fatty acid (FA) profile was determined in right (RV) and left (LV) ventricles. Adaptation to hypoxia decreased the concentration of diphosphatidylglycerol (DPG) in hypertrophied RV by 19% and in non-hypertrophied LV by 12% in comparison with normoxic controls. Chronically hypoxic hearts exhibited lower phospholipid n-6 polyunsaturated FA (PUFA) content mainly due to decreased linoleic acid (18:2n-6), which was opposed by increased n-3 PUFA mainly due to docosahexaenoic acid (22:6n-3) in phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI). The content of arachidonic acid (20:4n-6) was unchanged in total phospholipids, but in PC it was increased in both ventricles (by 22%) and in PE decreased in LV only (by 20%). Chronic hypoxia increased the un-saturation index of PC and PE in both ventricles. The content of monounsaturated FA (MUFA) was increased and 18:2n-6 decreased in DPG. The proportion of saturated FA was increased in PC and PI of hypoxic RV but not LV. The FA composition of phosphatidylserine was not altered in hypoxic ventricles. It is concluded that chronic hypoxia led to only minor changes in individual phospholipid concentration in rat ventricular myocardium, but markedly altered their FA profile. These changes, in particular the greater incorporation of n-3 PUFA into phospholipids and increased un-saturation index, may lead to a better preservation of membrane integrity and thereby contribute to improved ischemic tolerance of chronically hypoxic hearts.

[1]  S. C. Manchanda,et al.  Cardiovascular responsiveness to beta-adrenergic stimulation and blockade in chronic hypoxia. , 1975, The American journal of physiology.

[2]  T. Kenner Some comments on ventricular afterload , 1987, Basic Research in Cardiology.

[3]  M. Abeywardena,et al.  The influence of age and dietary fat in an animal model of sudden cardiac death. , 1989, Australian and New Zealand journal of medicine.

[4]  J. Richalet,et al.  Hypoxia-induced downregulation of beta-adrenergic receptors in rat heart. , 1992, Journal of applied physiology.

[5]  S. Gudbjarnason,et al.  Reversible alterations in fatty acid composition of heart muscle membrane phospholipids induced by epinephrine in rats fed different fats. , 1988, Journal of lipid research.

[6]  J. Widimský,et al.  The effect of beta adrenergic blockade on pulmonary hypertension, right ventricular hypertrophy and polycythaemia, induced in rats by intermittent high altitude hypoxia , 1978, Basic Research in Cardiology.

[7]  P. Molinoff,et al.  Effects of hypoxia on density of beta-adrenergic receptors. , 1981, Journal of applied physiology: respiratory, environmental and exercise physiology.

[8]  J. Charnock Antiarrhythmic effects of fish oils. , 1991, World review of nutrition and dietetics.

[9]  B. Lucchesi,et al.  The effect of dietary supplementation of fish oil on experimental myocardial infarction. , 1980, Prostaglandins.

[10]  C. E. Hock,et al.  Influence of dietary n-3 fatty acids on myocardial ischemia and reperfusion. , 1990, The American journal of physiology.

[11]  V. Pelouch,et al.  Activity of Cytochrome c Oxidase in the Right and Left Ventricular Myocardium of Male and Female Rats Exposed To Intermittent High Altitude Hypoxiaa , 1999, Annals of the New York Academy of Sciences.

[12]  S. Gudbjarnason,et al.  Reversible alterations in fatty acid profile of glycerophospholipids in rat heart muscle induced by repeated norepinephrine administration. , 1983, Biochimica et biophysica acta.

[13]  D. Das,et al.  Preconditioning of heart by repeated stunning: Adaptive modification of myocardial lipid membrane , 2004, Basic Research in Cardiology.

[14]  M. Nussbaum Dietary fish oil supplementation attenuates myocardial dysfunction and injury caused by global ischemia and reperfusion in isolated rat hearts. , 1994, JPEN. Journal of parenteral and enteral nutrition.

[15]  F. Oudot,et al.  Eicosanoid synthesis in cardiomyocytes: influence of hypoxia, reoxygenation, and polyunsaturated fatty acids. , 1995, The American journal of physiology.

[16]  F. Kolář Cardioprotective Effects of Chronic Hypoxia: Relation to Preconditioning , 1996 .

[17]  F. Kolář,et al.  Adaptation to high altitude hypoxia protects the rat heart against ischemia-induced arrhythmias. Involvement of mitochondrial K(ATP) channel. , 1999, Journal of molecular and cellular cardiology.

[18]  K. Iizuka,et al.  Phospholipid metabolism and prostacyclin synthesis in hypoxic myocytes. , 1991, Biochimica et biophysica acta.

[19]  M. B. Kelly,et al.  The modulation of protein kinase C activity by membrane lipid bilayer structure. , 1994, The Journal of biological chemistry.

[20]  P. Verdouw,et al.  Dietary fatty acids and myocardial function. , 1987, Basic research in cardiology.

[21]  B. O’Rourke,et al.  Effects of Adrenoceptor Blockade on Cardiac Hypertrophy and Myocardial Phospholipids , 1992, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[22]  J. Folch,et al.  A simple method for the isolation and purification of total lipides from animal tissues. , 1957, The Journal of biological chemistry.

[23]  J. Mehta,et al.  Long-term dietary fish oil supplementation protects against ischemia-reperfusion-induced myocardial dysfunction in isolated rat hearts. , 1993, American heart journal.

[24]  J. Mehta,et al.  Dietary fish oil supplementation attenuates myocardial dysfunction and injury caused by global ischemia and reperfusion in isolated rat hearts. , 1993, The Journal of nutrition.

[25]  R. Reneman,et al.  Fatty acid homeostasis in the normoxic and ischemic heart. , 1992, Physiological reviews.

[26]  B. O’Rourke,et al.  Altered phospholipid metabolism in pressure-overload hypertrophied hearts. , 1986, The American journal of physiology.

[27]  S. Fleischer,et al.  Two dimensional thin layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots , 1970, Lipids.

[28]  A. Simopoulos,et al.  Summary of the conference on the health effects of polyunsaturated fatty acids in seafoods. , 1986, The Journal of nutrition.

[29]  A. Bordoni,et al.  Evidence for a detectable delta-6-desaturase activity in rat heart microsomes: aging influence on enzyme activity. , 1993, Biochemical and biophysical research communications.

[30]  O. Koch,et al.  Liver and heart mitochondria in rats submitted to chronic hypobaric hypoxia. , 1988, The American journal of physiology.

[31]  A. Grynberg,et al.  In vitro study of docosahexaenoic acid incorporation into phosphatidylcholine by enzymes of rat heart , 1990, Molecular and Cellular Biochemistry.

[32]  S. Gudbjarnason,et al.  Modification of the fatty acid composition of rat heart sarcolemma with dietary cod liver oil, corn oil or butter. , 1988, Journal of molecular and cellular cardiology.

[33]  J. Remmers,et al.  Hypoxia: The Adaptations , 1988 .

[34]  M. Abeywardena,et al.  Differences in the fatty acid composition of atrial and ventricular phospholipids of rat heart following standard and lipid-supplemented diets. , 1983, Comparative biochemistry and physiology. B, Comparative biochemistry.

[35]  R. Capaldi,et al.  Diphosphatidylglycerol is required for optimal activity of beef heart cytochrome c oxidase. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[36]  A. Grynberg,et al.  Phospholipase a activity of cultured rat ventricular myocyte is affected by the nature of cellular polyunsaturated fatty acids , 1990, Lipids.

[37]  U. Mansmann,et al.  Heart mitochondria in rats submitted to chronic hypoxia. , 1999, Histology and histopathology.