Central role of connexin40 in the propagation of electrically activated vasodilation in mouse cremasteric arterioles in vivo

Circ Res. 2003 Apr 18;92(7):793-800. doi: 10.1161/01.RES.0000065918.90271.9A. Epub 2003 Mar 13.


When a short segment of arteriole is stimulated, vasomotor responses spread bidirectionally along the vessel axis purportedly via gap junctions. We used connexin40 knockout (Cx40-/-) mice to study vasomotor responses induced by 10-second trains of electrical stimulation (30 Hz, 1 ms, 30 to 50 V) in 2nd or 3rd order arterioles of the cremaster muscle. Measurements were made at the stimulation site (local) and at conducted sites (500, 1000, and 2000 microm upstream). In wild-type (Cx40+/+) animals, electrical stimulation evoked a local vasoconstriction and a conducted vasodilation that spread very rapidly along the vessel length without detectable decay. In Cx40-/- mice, the conducted dilation was converted into either vasoconstriction or a slowly developing vasodilation that decayed along the vessel length. Tetrodotoxin (TTX, 1 micromol/L) had no effect on the local vasoconstriction in either Cx40+/+ or Cx40-/- mice, but enhanced the conducted vasodilation in Cx40+/+ animals. In Cx40-/- mice, TTX abolished the conducted vasoconstriction when present and revealed a small vasodilation that decayed with distance. In the group of Cx40-/- mice in which electrical stimulation elicited a conducted vasodilation, TTX had no effect. Immunocytochemistry revealed Cx40 only in the endothelial layer of arterioles from Cx40+/+ mice and complete elimination of this connexin in the Cx40-/- animals. These results indicate that focal current stimulation causes vasoconstriction by a combination of perivascular nerve stimulation and smooth muscle activation. Moreover, electrical stimulation activates a nonneuronal, Cx40-dependent vasodilator response that spreads along the vessel length without decay.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abdominal Muscles / blood supply*
  • Animals
  • Arterioles / drug effects
  • Arterioles / innervation
  • Arterioles / physiology*
  • Connexins / analysis
  • Connexins / genetics
  • Connexins / physiology*
  • Electric Stimulation
  • Endothelium, Vascular / chemistry
  • Genotype
  • Immunohistochemistry
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Prazosin / pharmacology
  • Tetrodotoxin / pharmacology
  • Vasodilation / drug effects
  • Vasodilation / physiology*


  • Connexins
  • connexin 40
  • Tetrodotoxin
  • Prazosin