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Increased vascular sensitivity and connexin43 expression after sympathetic denervation
David P Slovut1, Shyamal H Mehta, Anne M Dorrance
1Department of Physiology, University of Michigan, Ann Arbor, MI, USA.
Cardiovascular Research
|April 20, 2004
Summary
Sympathetic denervation increases connexin43 (Cx43) expression in vascular smooth muscle. This heightened Cx43 contributes to increased oscillatory activity and heightened sensitivity to agonists in denervated arteries.
Area of Science:
- Vascular biology
- Cardiovascular physiology
- Molecular cardiology
Background:
- Arterial denervation leads to increased sensitivity to alpha-adrenergic agonists.
- Denervation is associated with enhanced oscillatory contractions in arteries.
- Increased gap junction expression may underlie these post-denervation changes.
Purpose of the Study:
- To investigate the impact of sympathetic denervation on connexin43 (Cx43) expression.
- To determine the effect of denervation on agonist-induced contractility in vascular smooth muscle (VSM).
Main Methods:
- Sympathetic denervation was induced using reserpine or phenol-glycerol.
- Vascular smooth muscle (VSM) contractions and Cx43 expression (mRNA and protein) were analyzed.
- Artery reactivity was assessed in response to norepinephrine (NE) and in Cx43 heterozygote deficient (KO) mice.
Main Results:
- Denervation significantly reduced the concentration for NE-induced contraction and increased oscillatory activity (OA).
- Cx43 mRNA and protein levels were significantly elevated following denervation.
- WT vessels exhibited greater cumulative OA than Cx43 KO vessels, indicating a role for Cx43.
Conclusions:
- Sympathetic denervation increases the expression of connexin43 (Cx43) in VSM.
- Elevated Cx43 expression contributes to increased spontaneous and agonist-induced oscillatory activity.
- Cx43 plays a critical role in the altered vascular contractility observed after denervation.