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

Abstract:

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 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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Chauhan S,Rahman A,Nilsson H,Clapp L,MacAllister R,Ahluwalia A

doi

10.1016/s0008-6363(02)00611-9

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

207-16

issue

1

eissn

0008-6363

issn

1755-3245

pii

S0008636302006119

journal_volume

57

pub_type

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