Increased vascular sensitivity and connexin43 expression after sympathetic denervation

Objective: Following denervation, arteries demonstrate a heightened sensitivity to a-adrenergic agonists and increased oscillatory contractions that may partly result from increased gap junction expression. Hence, we wanted to study the effect of sympathetic denervation on connexin43 (Cx43) expression and agonist-induced contractility in the vascular smooth muscle (VSM). Methods: Effects of denervation with reserpine (3 mg/kg/day, i.p.) or topical 5% phenol-glycerol on VSM contractions and expression of the gap junction Cx43 mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting for Cx43 protein were examined. Wistar-Kyoto (WKY) rat tail arteries were exposed to norepinephrine (NE) (10(-9) - 10(-5) M). Reactivity was also examined in the carotid arteries and thoracic aortas from Cx43 heterozygote deficient (KO) mice. Results: The concentration for NE-induced contraction was lower in reserpine- and phenol-treated vessels than controls (p < 0.05). NE-induced oscillatory activity (OA) was seen in 515 reserpine- and 5/8 phenol-treated vessels vs. 0/ 12 controls (p < 0.05). Spontaneous OA was observed more frequently in carotid and aortic rings from WT than Cx43 KO rings. Cumulative OA in response to a-adrenergic stimulation was significantly greater in WT carotid (429 +/- 101 vs. 128 +/- 7 mN s, p < 0.05) and aortic rings (337 +/- 85 vs. 134 +/- 11 mN s, p < 0.05) than in Cx43 KO rings. Following denervation, RT-PCR showed significantly increased levels of Cx43 mRNA (p < 0.05). Western blot analysis revealed near doubling of Cx43 protein (p < 0.05). Conclusion: We conclude that sympathetic denervation results in increased expression of Cx43, which in turn, contributes to increased spontaneous and agonist-induced OA in VSM. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.