Cardiovascular Research Advance Access [Accepted Manuscript] published online on July 1, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn178
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Blood pressure variability increases connexin expression in the vascular smooth muscle of rats
a Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
b Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
c Department of Physics and Chemistry, Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
* Corresponding author: Dr. Matheus L. Rocha - Laboratório de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. 14040-903 Ribeirão Preto, SP- Brazil. Fax: +55-16-36024880 / Phone: +55-16-36024704 E-mail address: rochaml{at}usp.br
Aims: Following sinoaortic denervation (SAD), isolated rat aortas present oscillatory contractions and demonstrate a heightened contraction for 
-adrenergic agonists. Our aim was to verify the effects of SAD on connexin43 (Cx43) expression and phenylephrine-induced contraction in isolated aortas.
Methods: Three days after surgery (SAD or sham operation), isolated aortic rings were exposed to phenylephrine and acetylcholine (0.1 nM to 10 µM) in the presence or absence of the gap junction blocker 18β-glycyrrhetinic acid (18β-GA, 100 µM). Vascular reactivity to potassium chloride (KCl, 4.7 to 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.
Results: Phenylephrine-induced contraction was higher in SAD rat aortas compared with the control. In the presence of 18β-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 18β-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).
Conclusion: 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.
Time for primary review: 49 days