Cardiology Letters 2011, 20(4):301-310

Alterations of myocardial NOS activity and connexin-43 expression in rats suffering from hypertension and hypertriglyceridemia are attenuated by omegy-3 fatty acids

Radosinska J^{1, 2}, Bacova B¹, Bernatova I³, Navarova J⁴, Benova T¹, Tribulova N¹

¹ Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia

² Institute of Physiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia

³ Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovakia, Centre of Excellence for Cardiovascular Research

⁴ Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia

Introduction: Our previous and others studies´ suggest that NO bioavailability and cell-to-cell coupling protein, connexin-43 (Cx43), are abnormal in diseased hearts of humans as well as experimental animals. Consequently, it can contribute to deterioration of heart function and occurrence of life-threatening arrhythmias.

Objective: We tested our hypothesis that the cardioprotective compounds, omega-3 PUFA, may be beneficial in hypertensive and hypertriglyceridemic rats in respect to disease-related abnormalities in NO production and Cx43 expression.

Methods: Myocardial nitric oxide synthase (NOS) activity and Cx43 expression were investigated in young and old spontaneously hypertensive rats (SHR), adult hereditary hypertriglyceridemic (HTG) rats, and age-matched healthy rats without and with omega-3 PUFA supplementation (30 mg/day/100g b.w) for 2 months.

Results: When compared to healthy rats myocardial NOS activity was significantly increased in young SHR (8.2 ± 1.16 vs. 1.37 ± 0.67 pmol/min/mg) as well as old SHR (3.21 ± 0.75 vs. 2.22 ± 0.56 pmol/min/mg) and to a much lesser extent in HTG rats, i.e., 1.87 ± 0.42 vs. 1.34 ± 0.1 pmol/min/mg. In parallel, there was a significant decline of total and phosphorylated forms of Cx43 in both groups of SHR while not in HTG rat hearts, in which the phosphorylated form of Cx43 was increased. Elevated NOS activity was suppressed (p<0.05) in young and old SHR supplemented with omega-3 PUFA and it was associated with up-regulation of Cx43. In contrast to SHR, elevation of NOS activity in HTG rat hearts was not affected by treatment with omega-3 PUFA. However, increase of phosphorylated form of Cx43 was suppressed.

Conclusions: There is an inverse relationship between myocardial NOS activity and Cx43 expression in SHR, though not HTG, rat hearts, and omega-3 PUFA modulate both NOS activity and Cx43 expression. Whether over-expression of inducible NOS might account for down-regulation of myocardial Cx43 and whether its up-regulation is associated with an increase of endothelial NOS should be explored by further study. Results point out the impairment of Cx43 mediated myocardial cell-to-cell communication due to hypertension and hypertriglyceridemia and its possible protection by compounds affecting the expression of Cx43. In addition, improvement of intercellular communication and consequently myocardial synchronization and diseased heart function is a major task in clinical practice.

Keywords: heart; nitric oxide synthase; connexin 43; omega-3 polyunsaturated fatty acids; spontaneously hypertensive rats; hereditary hypertriglyceridemic rats

Published: April 1, 2011  Show citation