Aortic connexin43 is decreased during hypertension induced by inhibition of nitric oxide synthase.
Connexin43 (Cx43), the predominant gap junction protein 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 of arterial hypertension induced by inhibition of nitric oxide synthase on the expression of Cx43 in aorta and heart as well as on the distensibility of the carotid artery. Administration of 0.4 g/L NG-nitro-L-arginine methyl ester (L-NAME) to rats in their drinking water for 4 weeks increased intra-arterial mean blood pressure, wall thickness of aorta and carotid artery (25%), and heart weight (17%). Analysis of heart mRNA demonstrated increased expression of the fetal skeletal alpha-actin and of atrial natriuretic peptide but not of Cx43. In contrast, Cx43 mRNA and protein were decreased by 50% in the aortas of L-NAME-treated rats that did not show increased carotid distensibility. Because these data contrasted with those obtained in the 2-kidney, 1 clip model of rat hypertension, which is characterized by increased arterial distensibility and Cx43 expression in aorta, we investigated by Western blot analysis the posttranslational modifications of Cx43. We found that Cx43 was more phosphorylated in the aorta of 2-kidney, 1 clip rats than in that of L-NAME or control rats, which indicated a differential regulation of Cx43 in different models of hypertension. The data suggest that the cell-to-cell communication mediated by Cx43 channels may help regulate the elasticity of the vascular wall.
Department of Internal Medicine, Division of Hypertension and Vascular Medicine, University Hospital, Lausanne, Switzerland. jhaeflig@chuv.hospvd.ch
J A
JA
Haefliger
P
P
Meda
A
A
Formenton
P
P
Wiesel
A
A
Zanchi
H R
HR
Brunner
P
P
Nicod
D
D
Hayoz
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006332:Cardiomegaly / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D018031:Connexin 43 / Q000032:analysis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000737:chemistry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D051381:Rats; D011921:Rats, Inbred WKY
D018031:Connexin 43; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester