EDHF mediates the relaxation of stretched canine femoral arteries to acetylcholine

To test the hypothesis that mechanically stretched arteries relax to endoth elium-derived vasodilators, we challenged endothelium-intact dog femoral ar tery rings stretched from 1 to 16 g total initial tension (active force and passive elastic) with 10(-6) M acetylcholine (ACh), an endothelium-depende nt dilator. The relaxation to 10(-6) M sodium nitroprusside (SNP), an endot helium-independent dilator, increased with the total initial tension. The r elaxation to ACh averaged approximately 65% of the relaxation to SNP at tot al initial tensions of 4 to 16 g. To determine the nature of the endothelia l-derived products involved, we compared the ACh-induced relaxation of stre tched rings (6.5 +/- 0.2 g total initial tension) with rings chemically con tracted with phenylephrine (Phe, 10(-7) to 10(-5) M) (6.5 +/- 0.3 g total i nitial tension). ACh-induced relaxation was evaluated before and after the inhibition of the synthesis of eicosanoids [cyclooxygenase (10(-5) M indome thacin) and lipoxygenase (10(-5) M nordihydroguariaretic acid)] and nitric oxide [nitric oxide synthase (10(-5) M N-w-nitro-L-arginine)]. The contribu tion of endothelium-derived hyperpolarizing factor (EDHF) was identified by blocking calcium-activated potassium channels (10(-8) M iberiotoxin). SNP (10(-6) M) relaxed stretched rings by 1.7 +/- 0.1 g and chemically-activate d rings by 4.8 +/- 0.2 g. ACh relaxed stretched rings to 73 +/- 3% of the S NP relaxation and this was only attenuated in the presence of iberiotoxin. ACh relaxed Phe-activated rings to 60 +/- 3% of the SNP relaxation. This re laxation was attenuated by inhibition of the synthesis of nitric oxide and (or) eicosanoids. Therefore, ACh relaxed stretched rings through the releas e of EDHF whereas the relaxation of chemically activated rings to ACh invol ved multiple endothelium-derived vasodilators.