Hypertension Differentially Affects the Expression of the Gap Junction Protein Connexin43 in Cardiac Myocytes and Aortic Smooth Muscle Cells

Connexin43-dependent mechanism modulates renin secretion and hypertension

“…We have previously reported that renin-dependent hypertension, which is experimentally induced by clipping of 1 renal artery in the 2-kidney, 1-clip (2K1C) model, is associated with a vesselspecific increase in the expression of Cx43 (25)(26)(27). Consistent with this view, the endothelium-specific ablation of Cx43 in at least some vessels resulted in either no change (28) or a drop of blood pressure (29).…”

“…We have previously reported that the renin-dependent hypertension that is experimentally induced by clipping of 1 renal artery in the 2K1C model is associated with a vessel-specific increase in the expression of Cx43 (25)(26)(27). These findings, the specific distribution of Cx43 between smooth muscle cells and selected ECs of vessels, and the regulation of Cx43 levels in both vascular endothelial and smooth muscle cells exposed to shear stress and other mechanical challenges (33)(34)(35)(36)(37) provide evidence that the cellto-cell communication mediated by Cx43 channels contributes to…”

“…Sham-operated mice were exposed to the same surgical manipulations, except the clipping. After surgery, all mice were kept on a regular diet with free access to water and were housed for 4 weeks at constant temperature and humidity, according to standard light/dark cycles (23,26,32). One day before sacrifice, the right carotid artery was exposed through a cervical incision, and isolated by blunt dissection.…”

Vascular Gap Junctions in Hypertension

“…In 2K1C and high-salt diet-induced hypertension, the vasodilation induced by acetylcholine (ACh) was not changed, but in these animals, the response was mainly mediated by an EDHF-dependent pathway instead of NO. 106,107 This change might be expected, because the expression of Cx43 is increased in the 2K1C model, 48,49 and this connexin is essential in the EC-VSMC coupling. 15 In contrast to the findings in the 2K1C animal, ACh-mediated vasodilation and the gap junction-dependent smooth muscle hyperpolarization were reduced in the SHR.…”

Gap Junction Proteins

“…32 It is interesting that in the few studies that have either measured transcription directly or evaluated mRNA stability through treatment with cycloheximide, the endothelial changes have been ascribed to altered mRNA stability (eg, see References 27,28,and 33), whereas the changes in smooth muscle have been shown to be transcriptional. 26 Comparably fewer in vivo studies have been performed to evaluate effects of vascular manipulations on connexin expression, although the findings in arterial smooth muscle cells have been striking: Cx43 expression was shown to be increased in several hypertensive models 34,35 and after balloon injury, 36 whereas reduced Cx43 expression resulted from hypercholesterolemia-induced atherosclerosis. 37 Gabriels and Paul 2 report that Cx43 is virtually absent in most regions of rodent aortic endothelium, except at sites in which branching or flow division is expected to create high turbulence, and that Cx43 expression is reciprocally related to that of Cx37.…”