NO contributes to EDHF-like responses in rat small arteries: a role for NO stores.
OBJECTIVE
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 microM), and indomethacin (Indo, 5 microM) in the absence or presence of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 microM), nitro-L-arginine (300 microM) or L-nitro-mono-methyl-arginine (L-NMMA, 300 microM). Addition of OxyHb (20 microM) or carboxy-PTIO (300 microM) produced a significant suppression of ACh-induced relaxations ( approximately 40%). 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.
Chauhan
Sharmila
S
Centre for Clinical Pharmacology, University College London, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK. s.chauhan@qmul.ac.uk
Rahman
Awahan
A
Nilsson
Holger
H
Clapp
Lucie
L
MacAllister
Raymond
R
Ahluwalia
Amrita
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000528:radiation effects; D006499:Hepatic Artery; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010042:Ouabain / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014466:Ultraviolet Rays; D014665:Vasodilator Agents / Q000494:pharmacology
D002317:Cardiovascular Agents; D010108:Oxyhemoglobins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D018999:Charybdotoxin; D001464:Barium; D009569:Nitric Oxide; D010042:Ouabain; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin