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 Nω-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 (C×43) in human umbilical vein endothelial cells (HUVEC) were compared. Results Endothelial C×43 was reduced by 35% and C×37 by 59% in hypertensive rats (P< .001). The reduction was recovered fully by carvedilol but only partially by atenolol (P< .05), although both drugs lowered the blood pressure to similar levels. C×40 remained stationary in all groups. In HUVEC, carvedilol (10 μg/mL) increased C×43 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 C×43. 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 C×43 and the effect is independent of its antioxidant activity.