© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
NO contributes to EDHF-like responses in rat small arteries: a role for NO stores
aCentre for Clinical Pharmacology, University College London, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK
bDepartment of Physiology, Aarhus University, Universiteitsparken 160, DK 8000 Aarhus C, Denmark
cDepartment of Clinical Pharmacology, Barts and The London, Charterhouse Square, London EC1M 6BQ, UK
s.chauhan{at}qmul.ac.uk
* Corresponding author. Department of Clinical Pharmacology, Barts and The London, Charterhouse Square, London EC1M 6BQ, UK. Tel.: +44-20-7882-3402; fax: +44-20-7882-3408.
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 NG-nitro-L-arginine methyl ester (L-NAME, 300 µM), and indomethacin (Indo, 5 µM) in the absence or presence of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 µM), nitro-L-arginine (300 µM) or L-nitro-mono-methyl-arginine (L-NMMA, 300 µM). Addition of OxyHb (20 µM) or carboxy-PTIO (300 µM) produced a significant suppression of ACh-induced relaxations (
40%). In L-NAME+Indo treated arteries ACh-induced hyperpolarisation (
16.3±2.1 mV, n=8) was significantly suppressed with the addition of OxyHb (10.2±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.
KEYWORDS Endothelial factors; K-channel; Membrane potential; Nitric oxide
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