Reduced expression of endothelial connexins 43 and 37 in hypertensive rats is rectified after 7-day carvedilol treatment

Background: The aim of this study was to clarify the response of endothelial connexins to hypertension and antihypertensive drugs. Methods: Rats remained normotensive (group 1, N = 10) or were made hypertensive using N-omega-nitro-L-arginine methyl ester (L-NAME) (groups 2 to 4, N = 10/group). Seven weeks later groups 3 and 4 were respectively fed atenolol or carvedilol daily for 7 days and the aortic endothelial gap junctions were analyzed. In parallel the effects of atenolol, carvedilol, labetalol, vitamin C, and vitamin E on connexin43 (Cx43) in human umbilical vein endothelial cells (HUVEC) were compared. Results: Endothelial Cx43 was reduced by 35% and Cx37 by 59% in hypertensive rats (P <.001). The reduction was recovered fully by carvedilol but only partially partially by atenolol (P <.05), although both drugs lowered the blood pressure to similar levels. Cx40 remained stationary in all groups. In HUVEC, carvedilol (10 mu g/mL) increased Cx43 protein expression by >70% (P <.01), whereas other drugs had minimal effects. The upregulation by carvedilol was associated with increased transcripts and decreased proteolysis of Cx43. Conclusions: The study showed that L-NAME-induced hypertension has differential effects on endothelial connexins, which respond variously to carvedilol and atenolol. In HUVEC carvedilol directly upregulates endothelial Cx43 and the effect is independent of its antioxidant activity.