Blood pressure variability increases connexin expression in the vascular smooth muscle of rats.
OBJECTIVE
Following sinoaortic denervation (SAD), isolated rat aortas present oscillatory contractions and demonstrate a heightened contraction for alpha-adrenergic agonists. Our aim was to verify the effects of SAD on connexin43 (Cx43) expression and phenylephrine-induced contraction in isolated aortas.


RESULTS
Three days after surgery (SAD or sham operation), isolated aortic rings were exposed to phenylephrine and acetylcholine (0.1-10 microM) in the presence or absence of the gap junction blocker 18beta-glycyrrhetinic acid (18beta-GA, 100 microM). Vascular reactivity to potassium chloride (KCl, 4.7-120 mM) was also examined. The incidence of rats presenting oscillatory contractions was measured. Effects of SAD on the vascular smooth muscle expression of the Cx43 mRNA by RT-PCR and western blotting for Cx43 protein were examined. Phenylephrine-induced contraction was higher in SAD rat aortas compared with the control. In the presence of 18beta-GA, the response to phenylephrine was similar in both groups. Oscillatory contractions were observed in 10/10 SAD rat aortas vs. 2/10 controls. Relaxing response to acetylcholine was similar in both groups, but in the presence of 18beta-GA, the response to acetylcholine decreased significantly in the sham-operated group (82.7 +/- 7.6% reduction of relaxation), whereas a half-maximal relaxation (reduction of 46.2 +/- 5.3%) took place in SAD rat aortas. KCl-induced contraction was similar in both groups. Following SAD, RT-PCR revealed significantly increased levels of Cx43 mRNA (9.85 fold, P < 0.01). Western blot analysis revealed greater levels of Cx43 protein (P < 0.05).


CONCLUSIONS
Blood pressure variability evoked by SAD leads to increased expression of Cx43, which could contribute to enhanced phenylephrine-induced contraction and oscillatory activity in isolated aortas.
Rocha
Matheus L
ML
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Av do café, s/n, Ribeirão Preto, Brazil. rochaml@usp.br
Kihara
Alexandre H
AH
Davel
Ana P
AP
Britto
Luiz R G
LR
Rossoni
Luciana V
LV
Bendhack
Lusiane M
LM
D000818:Animals; D001013:Aorta, Thoracic / Q000294:innervation / Q000378:metabolism*; D001794:Blood Pressure; D002450:Cell Communication; D018031:Connexin 43 / Q000378:metabolism*; D003714:Denervation; D017629:Gap Junctions / Q000378:metabolism*; D015870:Gene Expression; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
D018031:Connexin 43