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

Autor: Brian R. Duling, Kathy H. Day, Xavier F. Figueroa, David N. Damon, Daniel A. Goodenough, David L. Paul, Alexander M. Simon
Rok vydání: 2003
Předmět:
Zdroj: Circulation research. 92(7)
ISSN: 1524-4571
Popis: 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 μm 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 μmol/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.
Databáze: OpenAIRE