Acetylcholine-induced vasodilation may depend entirely upon NO in the femoral artery of young piglets

• 1. To characterize agonist-induced relaxation in femoral artery rings from young piglets, we compared the effect of a NOS-inhibitor N?-nitro-L-arginine (L-NOARG), an NO-inactivator oxyhaemoglobin (HbO) and a soluble guanyl cyclase(sGC)-inhibitor 1H-[1,2,4]Oxadiazolo-[4,3,-a]quinoxalin-1-one (ODQ) on acetylcholine(ACh)-induced relaxation. The involvement of K+ channel activation was studied on relaxations induced by ACh, the two NO donors sodium nitroprusside (SNP) and diethylamine (DEA) NONOate, and the cell membrane permeable guanosine 3'5' cyclic monophosphate (cGMP) analogue 8-Br-cGMP. 2. Full reversal of phenylephrine-mediated precontraction was induced by ACh (1 nM-1 ╡M) (pD2 8.2▒0.01 and Rmax 98.7▒0.3%). L-NOARG (100 ╡M) partly inhibited relaxation (pD2 7.4▒0.02 and Rmax 49.6▒0.8%). The L-NOARG/indomethacin(IM)-resistant response displayed characteristics typical for endothelium-derived hyperpolarizing factor (EDHF), being sensitive to a combination of the K+ channel blockers charybdotoxin (CTX) (0.1 ╡M) and apamin (0.3 ╡M). 3. ODQ (10 ╡M) abolished relaxations induced by ACh and SNP. L-NOARG/IM-resistant relaxations to ACh were abolished by HbO (20 ╡M). 4. Ouabain (1 ╡M) significantly inhibited ACh-induced L-NOARG/IM-resistant relaxations and relaxations induced by SNP (10 ╡M) and 8-Br-cGMP (0.1 mM). A combination of ouabain and Ba2+ (30 ╡M) almost abolished L-NOARG/IM-resistant ACh-induced relaxation (Rmax 7.7▒2.5% vs 23.4▒6.4%, with and without Ba2+, respectively, P<0.05). 5. The present study demonstrates that in femoral artery rings from young piglets, despite an L-NOARG/IM-resistant component sensitive to K+ channel blockade with CTX and apamin, ACh-induced relaxation is abolished by sGC-inhibition or a combination of L-NOARG and HbO. These findings suggest that relaxation can be fully explained by the NO/cGMP pathway.

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