Increased vascular sensitivity and connexin43 expression after sympathetic denervation.
OBJECTIVE
Following denervation, arteries demonstrate a heightened sensitivity to alpha-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 5/5 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 alpha-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).


CONCLUSIONS
We conclude that sympathetic denervation results in increased expression of Cx43, which in turn, contributes to increased spontaneous and agonist-induced OA in VSM.
Slovut
David P
DP
Department of Physiology, University of Michigan, Ann Arbor, MI, USA.
Mehta
Shyamal H
SH
Dorrance
Anne M
AM
Brosius
Frank C
FC
Watts
Stephanie W
SW
Webb
R Clinton
RC
D000818:Animals; D001011:Aorta; D001158:Arteries; D018031:Connexin 43 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010636:Phenols; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D012110:Reserpine; D013562:Sympathectomy; D013623:Tail / Q000098:blood supply
D018031:Connexin 43; D010636:Phenols; D012333:RNA, Messenger; D012110:Reserpine; D009638:Norepinephrine