title: Central role of connexin40 in the propagation of electrically activated vasodilation in mouse cremasteric arterioles in vivo.
abstract: 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.
authors.affiliation: Dept of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, PO Box 800736, Charlottesville, Va 22908-0736, USA. brd@virginia.edu
authors.forename: Xavier F
authors.initials: XF
authors.lastname: Figueroa
authors.forename: David L
authors.initials: DL
authors.lastname: Paul
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Simon
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Goodenough
authors.forename: Kathy H
authors.initials: KH
authors.lastname: Day
authors.forename: David N
authors.initials: DN
authors.lastname: Damon
authors.forename: Brian R
authors.initials: BR
authors.lastname: Duling
mesh_terms: D000009:Abdominal Muscles / Q000098:blood supply*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D017630:Connexins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000737:chemistry; D005838:Genotype; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011224:Prazosin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D011224:Prazosin; D013779:Tetrodotoxin; D000097003:Gap Junction alpha-5 Protein