In vitro simultaneous measurements of relaxation and nitric oxide concentration in rat superior mesenteric artery

1. The relationship between nitric oxide (NO) concentration measured with a n NO-specific microelectrode and endothelium-dependent relaxation was inves tigated in isolated rat superior mesenteric artery contracted with 1 mu M n oradrenaline. 2. Acetylcholine (10 mu M) induced endothelium-dependent simultaneous incre ases in luminal NO concentration of 21 +/- 6 nM, and relaxations with pD(2) values and maximum of 6.95 +/- 0.32 and 97.5 +/- 0.7% (n = 7), respectivel y. An inhibitor of NO synthase, N-G-nitro-L-arginine (L-NOARG, 100 mu M) in hibited the relaxations and increases in NO concentration induced by acetyl choline. 3. Oxyhaemoglobin (10 mu M) reversed the relaxations and increases in NO co ncentrations induced by acetylcholine, S-nitroso-N-acetylpenicillamine (SNA P) and S-morpholino-sydnonimine (SIN-1), but not the relaxations induced wi th forskolin. Oxyhaemoglobin also decreased the NO concentration below base line level. 4. In the presence of L-NOARG (100 mu M), a small relaxation to acetylcholi ne (10 mu M) of noradrenaline-contracted segments was still seen; oxyhaemog obin inhibited this relaxation and decreased the NO concentration by 14 +/- 4 nM (n = 4). 5. The NO concentration-relaxation relationship for acetylcholine resembled that for SNAP and SIN-1 more than for authentic NO. Thus while 7-17 nM NO induced half-maximal relaxations in response to SNAP or SIN-1, 378 +/- 129 nM NO (n = 4) was needed for half-maximal relaxation to authentic NO. 6. The present study provides direct evidence that the relaxation of the ra t superior mesenteric artery with the endothelium-dependent vasodilator ace tylcholine is correlated to the endogeneous release of NO. The study also s uggests that NO mediates the L-NOARG-resistant relaxations in this artery, and that there is a basal NO release.