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Hypertension alters expression of connexin-43 (Cx43) in cardiovascular system. The aim of the study was to investigate the effect of omega-3 polyunsaturated fatty acids (30 mg/day for 2 months) on expression of Cx43 in the aorta of 1-year-old male spontaneously hypertensive rats (SHR). Spatial distribution and expression of Cx43 in aortic wall of SHR and age-matched Lewis rats were determined by immunofluorescent method and Western blot. NO synthase (NOS) activity and endothelium-dependent relaxation of the aorta were measured as well. Immunofluorescent pattern of Cx43 was identified in endothelial and smooth muscle cells of the aorta of all experimental groups studied. However, local decrease in the number and intensity of fluorescent spots and reduced phosphorylation of Cx43 were observed in SHR in contrast to normotensive LEW. Omega-3 fatty acid diet increased Cx43 immunolabeling in endothelium and media of SHR comparing to untreated ones. Parallel, 3-fatty acids significantly elevated phosphorylation of Cx43 in the aorta of SHR (p<0.001). Despite the omega-3 fatty acids reduced blood pressure and stimulated aortic NOS activity in SHR, endothelium-dependent relaxation of the aorta did not significantly change. Results indicate that the aorta of old SHR might partially benefit from 3-PUFA supplementation due to increased Cx43 phosphorylation, NOS activity and decreased blood pressure.
We examined whether thyroid hormones affect myocardial -PKC signalling, downstream target substrate, connexin-43 (Cx43) and arrhythmogenesis in non-diabetic and diabetic rats. Diabetes was induced by a single streptozotocin injection (50mg/kg, i.v.). Triiodothyronine (T3) was applied by gavage (1µg/kg of body weight for 10 days) to 4 weeks and 9 weeks diabetic and age-matched non-diabetic rats. Western blot analysis of Cx43 and -PKC, immunofluorescence of Cx43, ultrastructure of cardiomyocytes and myocardial conduction velocity were performed. Isolated perfused heart preparation was used to test ventricular fibrillation susceptibility. T3 significantly decreased -PKC expression in non-diabetic and suppressed in diabetic rat heart ventricles. Decline of -PKC signalling was associated with decrease of Cx43 phosphorylation in diabetic and to a greater extent in non-diabetic rat hearts. However, conduction velocity was significantly decreased in diabetic while enhanced due to T3 and increased in non-diabetic T3-treated rat heart ventricles compared to non-treated. T3-induced down-regulation of Cx43 was associated with increased cardiac propensity to ventricular fibrillation. Findings indicate that activation of -PKC signalling linked with phosphorylation of Cx43 is one of the mechanisms involved in the adaptation of the heart to hyperglycemia. Suppression of -PKC and Cx43 phosphorylation by T3 abolish benefit of adaptation rendering the heart prone to lethal arrhythmias.
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