Agonist induced endothelium-dependent dilation is caused by the release of NO, PGI2 and an endothelium derived hyperpolarizing factor (EDHF). However, EDHF may be simple charge transfer through myoendothelial gap junctions (MGJ) composed of connexins (Cx). We studied dilation in preconstricted (NE, 1mM) small arteries (SA, gracilis artery) of wildtype (wt) and Cx40- deficient mice (Cx40-/-) to analyse the contribution of MGJ in EDHF-type dilations in vivo and in vitro.

ACh-induced dilation (1 mM) was only slightly reduced after inhibition of NOS and COX (L-NA and indomethacin, L+I, from 71±5 to 44±7%) under isometric conditions in wt. The remaining response was abrogated by a high K+ solution (50mM). In Cx40-/-

vessels, the dilation of SA was attenuated already under control conditions as compared to wt (41±11 vs. 71±5%) and the remaining response was abrogated by L+I (-17±14%). However, if this vessel was studied in vivo the dilations in wt and Cx40-/- were indistinguishable before and after L+I.

EDHF is the main mediator of ACh-dilations in small arteries. Cx40 is crucial for EDHF-type dilation in vitro suggesting that MGJ mediate the dilation and Cx40 is an essential component. The intact EDHF-type dilation in Cx40-/- in vivo suggests that under these conditions a different mechanism transmits the EDHF- type dilation that is independent of MGJ and Cx40.