当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > Chronic nitroglycerine administration reduces endothelial nitric oxide production in rabbit mesenteric resistance artery.

Chronic nitroglycerine administration reduces endothelial nitric oxide production in rabbit mesenteric resistance artery.

Abstract：

:We investigated whether 10 days' in vivo treatment with nitroglycerine (NTG) would inhibit nitric oxide production by the endothelial cells of resistance arteries ex vivo and, if so, what the underlying mechanism might be. ACh increased the intracellular nitric oxide concentration ([NO]i; estimated using the nitric oxide-sensitive fluorescent dye diaminofluorescein-2) within the endothelial cells of rabbit mesenteric resistance arteries. This effect was significantly smaller in arteries isolated from NTG-treated rabbits than in those from control rabbits. The reduction in endothelial [NO]i in NTG-treated rabbits was prevented when olmesartan (blocker of type 1 angiotensin II receptors (AT1Rs)) was coadministered in vivo with NTG and also when the superoxide scavenger manganese (III) tetrakis-(4-benzoic acid) porphyrin (Mn-TBAP), the protein kinase C (PKC) inhibitor GF109203X or L-arginine (with or without the active form of folate (5-methyltetrahydrofolate)) was incubated with the arteries in vitro. Endothelial cell superoxide production (estimated by ethidium fluorescence) was greatly increased in arteries from NTG-treated rabbits. This was normalized by in vivo coadministration of olmesartan with NTG and also by in vitro application of Mn-TBAP or GF109203X (but not of 5-methyltetrahydrofolate+L-arginine). ACh increased the intracellular Ca2+ concentration (estimated using the Ca2+-sensitive dye Fura 2) within endothelial cells, the increase being not significantly different between NTG-treated rabbits and control rabbits. We conclude that in NTG-treated rabbits, endothelial nitric oxide production in mesenteric resistance arteries is reduced, possibly through a reduction in the bioavailability of L-arginine via an action mediated by superoxide. Activation of the AT1R-PKC pathway may be involved in increasing superoxide production.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Yamamoto T,Kajikuri J,Watanabe Y,Suzuki Y,Suzumori K,Itoh T

doi

10.1038/sj.bjp.0706365

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

534-42

issue

eissn

0007-1188

issn

1476-5381

pii

0706365

journal_volume

146

pub_type

杂志文章

在线工具

Chronic nitroglycerine administration reduces endothelial nitric oxide production in rabbit mesenteric resistance artery.