Chronic hypertension alters the expression of Cx43 in cardiovascular muscle cells

Connexin43 (Cx43), the predominant gap junction protein of muscle cells in vessels and heart, is involved in the control of cell-to-cell communication and is thought to modulate the contractility of the vascular wall and the electrical coupling of cardiac myocytes. We have investigated the effects o f arterial hypertension on the expression of Cx43 in aorta and heart in thr ee different models of experimental Heart hypertension. Rats were made hype rtensive either by clipping one renal artery (two kidney, one-clip renal (2 K, 1C) model) by administration of deoxycorticosterone and salt (DOCA-salt model) or by inhibiting nitric oxide synthase with N-G-nitro-L-arginine met hyl ester (L-NAME model). After 4 weeks, rats of the three models showed a similar increase in intra-arterial mean blood pressure and in the thickness of the walls of both aorta and heart. Analysis of heart mRNA demonstrated no change in Cx43 expression in the three models compared to their respecti ve controls. The same 2K,1C and DOCA-salt hypertensive animals expressed tw ice more Cx43 in aorta, and the 2K,1C rats showed an increase in arterial d istensibility. In contrast, the aortae of L-NAME hypertensive rats were cha racterized by a 50% decrease in Cx43 and the carotid arteries did not show increased distensibility. Western blot analysis indicated that Cx43 was mor e phosphorylated in the aortae of 2K,1C rats than in those of L-NAME or con trol rats, indicating a differential regulation of aortic Cx43 in different models of hypertension. The data suggest that localized mechanical forces induced by hypertension affect Cx43 expression and that the cell-to-cell co mmunication mediated by Cx43 channels may contribute to regulating the elas ticity of the vascular wall.