Abstract:
:The cardiovascular and biochemical responses during acute oxidative stress induced by D,L-buthionine-(S,R)-sulfoximine (BSO) were investigated in Sprague-Dawley rats. Mean arterial pressure, heart rate and vascular reactivity were measured after subcutaneous injection of BSO (4 mmol/kg). Control rats received saline. Levels of GSH and GSSG in blood and tissues as well as renal superoxide were determined. Nitric oxide, prostacyclin and thromboxane A(2) in plasma and aorta, and isoprostane in plasma were also measured. Blood pressure was elevated at 24 h (121+/-2 vs. 104+/-2 mm Hg), with increased reactivity to phenylephrine (by a 59+/-4 vs. 45+/-2 mm Hg change), and impaired response to sodium nitroprusside (by a -35+/-2 vs. -63+/-2 mm Hg change), P<0.05. The GSH:GSSG ratio was reduced at 8 and 24 h in blood (4.1+/-0.6 and 5.1+/-0.3, respectively, vs. 8.5+/-0.2), and at 8 h in the aorta (1.0+/-0.2 vs. 2.9+/-0.5), heart (1.6+/-0.3 vs. 2.3+/-0.1) and kidney (2.1+/-0.2 vs. 3.7+/-0.4), P<0.05. Superoxide fluorescence was increased at 24 h via NADH (4131+/-194 vs. 2853+/-199), NADPH (2874+/-272 vs.1479+/-257) and succinate (2475+/-133 vs. 1594+/-2150), P<0.05. Plasma prostacyclin was reduced at 8 and 24 h (36+/-4 and 52+/-13, respectively, vs. 310+/-44 pg/ml), P<0.001, whereas nitric oxide was reduced at 24 h (6.4+/-1 vs. 22+/-2 microM), P<0.01. Also at 24 h, thromboxane A(2) was increased both in plasma (374+/-154 vs. 61+/-10 pg/ml) and the aorta (174.4+/-38 vs. 27+/-3.4 pg/mg), P<0.05. Thus, acute BSO-induced oxidative stress alters blood pressure and endothelial function by mechanisms involving increased plasma levels and aortic release of thromboxane A(2) and reduced nitric oxide and prostacyclin.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Ganafa AA,Socci RR,Eatman D,Silvestrova N,Abukhalaf IK,Bayorh MAdoi
10.1016/s0014-2999(02)02500-1keywords:
subject
Has Abstractpub_date
2002-11-15 00:00:00pages
217-23issue
2-3eissn
0014-2999issn
1879-0712pii
S0014299902025001journal_volume
454pub_type
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