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Role of oxidative stress and nitric oxide in regulation of spontaneous tone in aorta of DOCA‐salt hypertensive rats
Author(s) -
Ghosh Mahua,
Wang Hui Di,
McNeill J Robert
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705557
Subject(s) - apocynin , superoxide , nitric oxide , endocrinology , medicine , chemistry , endothelium , aorta , nitric oxide synthase , superoxide dismutase , nad(p)h oxidase , nicotinamide adenine dinucleotide phosphate , sodium nitroprusside , nadph oxidase , oxidative stress , oxidase test , biochemistry , enzyme
The roles of nitric oxide (NO), superoxide anion (O 2 − ), and hydrogen peroxide (H 2 O 2 ) in the modulation of spontaneous tone were investigated in isolated aorta from deoxycorticosterone acetate (DOCA)‐salt hypertensive rats. Increases in preload from 1 to 5 g were accompanied by increases in spontaneous tone in aortic rings from DOCA‐salt hypertensive rats but not from SHAM‐normotensive rats. Tone was higher in endothelium‐denuded aortic rings than in endothelium‐intact vessels. Inhibition of nitric oxide synthase (NOS) with 300 μ M N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME) increased spontaneous tone. Basal O 2 − generation was higher in aortic rings from DOCA‐salt hypertensive rats than in those from SHAM‐normotensive rats. Stretch increased O 2 − levels even further in the DOCA‐salt group. In rings isolated from DOCA‐salt hypertensive rats, administration of the O 2 − scavenger, superoxide dismutase (SOD, 150 U ml −1 ), or the nicotinamide adenine dinucleotide phosphate (NADPH)‐oxidase inhibitor, apocynin (100 μ M ), completely abolished the development of spontaneous tone in endothelium‐intact aortic rings but not in endothelium‐denuded or in L ‐NAME‐treated rings. SOD and apocynin decreased the generation of O 2 − in endothelium‐intact, endothelium‐denuded, and L ‐NAME‐treated aortic rings. Oral treatment of DOCA‐salt hypertensive rats with the O 2 − scavengers, tempol or tiron, or with apocynin for 3 weeks prevented the development of hypertension and abolished the increases in O 2 − generation and spontaneous tone. Administration of catalase (1000 U ml −1 ) to aortic rings increased spontaneous tone in vessels from DOCA‐salt hypertensive rats. Administration of the cyclooxygenase (COX) inhibitor, valeroyl salicylate, or the thromboxane/prostaglandin antagonist, SQ 29548, to aortic rings abolished tone. The results suggest that NO plays a major role in preventing the generation of spontaneous tone in isolated aortic rings from DOCA‐salt hypertensive rats. NADPH‐oxidase‐derived O 2 − enhanced spontaneous tone by inactivating NO. Endogenous H 2 O 2 appears to mitigate the increase in tone. In addition, a COX component may also contribute to spontaneous tone.British Journal of Pharmacology (2004) 141 , 562–573. doi: 10.1038/sj.bjp.0705557