Endothelium-dependent dilators like acetylcholine (ACh) act via the release of NO, PGI2 and EDHF. However, their relevance may vary in vessels with different functions. We studied ACh-dilations in isolated precontracted vessels of mice using pressure-or wire-myography. We also tested the potential role of myoendothelial coupling using mice deficient for the gap junction protein connexin40 (Cx40-/-).

ACh dilated all arteries concentration-dependently, amounting to 56±9% in femoral (fem, ~220 mm), 53±7% in mesenteric (mes, ~200 mm) and 68±11% in gracilis artery (gra, ~130 mm) at 0.3 mM ACh. Dilations were abrogated after inhibition of NOS and COX (L-NA and indomethacin, L+I) in fem and mes. Likewise, the ACh-dilation (78±6%, fem) was abrogated in Cx40-/- by L+I. In contrast, the dilation in gra was only slightly reduced by L+I (to 48±9%). This was also observed under isobaric conditions. The remaining response was abrogated by high K+ (50 mM). L+I did not affect NO-induced dilations (SNP). However, high K+ strongly reduced SNP-dilations in fem, but not in mes and gra.

In conclusion, EDHF is not a mediator of ACh-dilation in conducting vessels, in which NO and PGI2 dominate. In contrast, EDHF is the main player in small arteries. Myoendothelial coupling seems to be not decisive in larger vessels as judged by the data obtained in Cx40-deficient mice.