NO contributes to EDHF-like responses in rat small arteries: a role for NO stores

Objectives: Responses to EDHF are usually characterised in the presence of nitric oxide synthase (NOS) and cyclooxygenase (COX) inhibitors. The contribution of NO to endothelium-dependent relaxation in the presence of NOS inhibitors was assessed using NO scavengers with the objective of testing (i) whether any residual NO produces endothelium-dependent relaxation in a manner similar to EDHF and (ii) to identify the source of the residual NO. Methods: Small rat hepatic and mesenteric arteries were mounted in a tension myograph for either isometric or membrane potential measurements. Results: Relaxation to ACh was unaffected by pre-treatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 300 muM), and indomethacin (Indo, 5 muM) in the absence or presence of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin- 1-one (ODQ, 1 muM), nitro-L-arginine (300 muM) or L-nitro-mono-methyl-arginine (L-NMMA, 300 muM). Addition of OxyHb (20 muM) or carboxy-PTIO (300 muM) produced a significant suppression of ACh-induced relaxations ( approximate to40%). In L-NAME+Indo treated arteries ACh-induced hyperpolarisation (Delta16.3+/-2.1 mV, n=8) was significantly suppressed with the addition of OxyHb (Delta10.2+/-1.6 mV, n=12). ACh-induced relaxation, in the presence Of L-NAME+Indo+OxyHb, was abolished by raised extracellular K(+), or the combination of charybdotoxin (CTX, 100 nM)+apamin (100 nM). In contrast whilst L-NAME+indo +barium+ ouabain suppressed ACh-induced relaxation, the presence of OxyHb had no additional effect. Ultraviolet light induced a relaxation in arteries treated with L-NMMA+Indo (37.0+/-5.2%, n=9) which was sensitive to OxyHb (15.2+/-10.9%, n=4), and barium+ouabain (6.39+/-2.7%, n=4), but not CTX+apamin (37.8+/-2.4%, n=4). Conclusions: These findings suggest that NO contributes significantly to the "EDHF-like" response seen in rat small arteries and that the source of this NO may be preformed vascular stores. (C) 2002 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.