Irbesartan lowers superoxide levels and increases nitric oxide bioavailability in blood vessels from spontaneously hypertensive stroke-prone rats

Brosnan, M J; Hamilton, Carlene A.; Graham, Delyth; Lygate, Craig A.; Jardine, Emma; Dominiczak, Anna F.

doi:10.1097/00004872-200202000-00018

Cited by 67 publications

(34 citation statements)

References 29 publications

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“…We have previously validated this method to calculate NO bioavailability in rat carotid arteries infused with genes encoding NO synthase and superoxide dismutase 5,22 and to investigate effects of antihypertensive drugs on NO bioavailability in vivo and in vitro. 23 When expressed in this format, the apocynin-induced increases in NO bioavailability were greater than those observed in any of the previous studies and were greater that that achieved by scavenging of O 2 Ϫ with PEGSOD in the present study. When arteries from the 3-month-old SHRSP and WKY were compared, no differences were observed in NAD(P)Hstimulated O 2 Ϫ generation, apocynin inhibition of this O 2 Ϫ generation, or levels of expression of mRNA for the membrane-integrated components of the NAD(P)H oxidase system.…”

Section: Discussioncontrasting

confidence: 59%

NAD(P)H Oxidase Inhibition Improves Endothelial Function in Rat and Human Blood Vessels

et al. 2002

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Abstract-The NO/superoxide (O 2Ϫ ) balance is a key regulator of endothelial function. O 2 Ϫ levels are elevated in many forms of cardiovascular disease; therefore, decreasing O 2 Ϫ should improve endothelial function. To explore this hypothesis, internal mammary arteries and saphenous veins, obtained from patients undergoing coronary artery revascularization, and aortic and carotid arteries from Wistar-Kyoto and spontaneously hypertensive stroke-prone rats were incubated with O 2 Ϫ dismutase or NAD(P)H oxidase inhibitors. O 2 Ϫ levels were measured using lucigenin chemiluminescence; NO bioavailability was assessed in organ chambers; and mRNA expression of NAD(P)H oxidase components was quantified by use of a Light Cycler. In rat arteries, phenylarsine oxide, 4-(2-aminoethyl)-benzenesulfanyl fluoride, and apocynin all decreased NADH-stimulated O 2 Ϫ production, but only apocynin increased NO bioavailability. In human internal mammary arteries and saphenous veins, apocynin decreased NAD(P)H-stimulated O 2 Ϫ generation and caused vasorelaxation that was endothelium dependent and reversed on addition of the NO synthase inhibitor N G -nitro-L-arginine methyl ester. In addition, it increased NO production from cultured human endothelial saphenous vein cells. Polyethylene-glycolated O 2 Ϫ dismutase also increased NO bioavailability in rat carotid arteries and human blood vessels, but the effects were smaller than those observed with apocynin. NADH-generated O 2 Ϫ and mRNA expression of p22 phox , gp91 phox , and nox-1 were comparable between the 2 strains of rat. This is the first study to demonstrate pharmacological effects of apocynin in human blood vessels. The increases in NO bioavailability shown here suggest that the NAD(P)H oxidase pathway may be a novel target for drug intervention in cardiovascular disease.

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Section: Discussioncontrasting

confidence: 59%

NAD(P)H Oxidase Inhibition Improves Endothelial Function in Rat and Human Blood Vessels

et al. 2002

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“…A recent study in spontaneously hypertensive rats supports this observation (31). We used norepinephrine as a control because it results in a reduction of FBF similar to that by angiotensin II, thereby controlling for the nonspecific effects of decreased FBF.…”

Section: Fig 2 (A) Response Of Fbf To Acetylcholine (Ach) Before (Wmentioning

confidence: 64%

“…Endothelial vasodilator function is influenced by a balance between the production of NO and superoxide anions (6,7,29). Recent studies in animals suggest that an imbalance occurs due to decreased bioavailability of NO from either decreased production of NO by endothelial cells or increased degradation of NO by oxygen-derived free radicals (5,(30)(31)(32). NO has a very short half-life (from 0.5 to 5 s) and is rapidly broken down by superoxide anions under physiologic conditions (33).…”

Section: Discussionmentioning

confidence: 99%

Vitamin C Improves Attenuated Angiotensin II-Induced Endothelium-Dependent Vasodilation in Human Forearm Vessels

et al. 2003

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Endothelial dysfunction might be related to an increase in superoxide anion production in patients with hypertension, hypercholesterolemia, diabetes mellitus, and heart failure. Studies in animal models indicate that angiotensin II increases superoxide anion production by vascular tissues. We examined whether angiotensin II attenuates endothelium-dependent vasodilation via an increase in superoxide anion production in human forearm vessels in vivo.

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“…7,8,15 Endothelial function is directly affected by nitric oxide bioavailability, and its dysfunction is associated with oxidative stress induced by angiotensin II. 16,17 In an earlier report, although losartan and trichlormethiazide at equivalent hypotensive doses were administered for 2 weeks in SHR-SP, the mRNA levels of NADPH oxidase subunits and oxidative stress were significantly reduced by losartan, but not by trichlormethiazide. 18 Pu et al 19 showed that valsartan and hydralazine showed the same hypotensive effect in SHR-SP, but that valsartan, but not hydralazine, reduced endothelial dysfunction.…”

Section: Discussionmentioning

confidence: 93%

Significance of angiotensin II receptor blockers with high affinity to angiotensin II type 1 receptors for vascular protection in rats

Jin

Ikeda²,

Saito³

et al. 2009

Hypertens Res

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Angiotensin II receptor blockers (ARBs) vary in their binding affinities to angiotensin II type 1 (AT 1 ) receptors in in vitro experiments. We compared a high-affinity ARB, olmesartan, and a low-affinity ARB, valsartan, in terms of their vascular protective effects in stroke-prone spontaneously hypertensive rats (SHR-SP). Blood pressure was equally reduced by placebo, olmesartan (1 mg kg À1 ) and valsartan (3 mg kg À1 ) daily for 2 weeks. In another experiment, 12-week-old SHR-SP were fed 8% salt, and olmesartan (1 mg kg À1 ), valsartan (3 mg kg À1 ) or placebo were administered daily until a survival rate of 60% was reached. In the experiment using SHR-SP, the reduction of acetylcholine-induced vascular relaxation and the increase of p22 phox expression in the placebo-treated group were significantly attenuated by olmesartan and valsartan, but this attenuation was significantly greater for olmesartan. In immunohistological analysis, all areas positive for angiotensin II, p22 phox and 4-hydroxy-2-nonenal were significantly reduced by olmesartan and valsartan, but again this reduction was significantly greater for olmesartan. In salt-loaded SHR-SP, the number of days to reach a 60% survival rate was 25 and 42 in placebo and valsartantreated rats, respectively, and this represented a significant difference. The survival rate in olmesartan-treated rats was 95% at day 42, when valsartan-treated rats reached 60% survival, and this difference was also significant. In the surviving rats, olmesartan, but not valsartan, augmented acetylcholine-induced vascular relaxation and attenuated vascular p22 phox expression. Thus, heterogeneity in binding affinity to AT 1 receptors among ARBs may result in different degrees of vascular protection and lifespan extension.

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Irbesartan lowers superoxide levels and increases nitric oxide bioavailability in blood vessels from spontaneously hypertensive stroke-prone rats

Abstract: These studies support the hypothesis that AT1 receptor blockade has beneficial effects on superoxide production and nitric oxide bioavailability above that of other classes of antihypertensive agents. Reduced expression of components of the NAD(P)H oxidase may contribute to these effects.

Cited by 67 publications

References 29 publications

NAD(P)H Oxidase Inhibition Improves Endothelial Function in Rat and Human Blood Vessels

NAD(P)H Oxidase Inhibition Improves Endothelial Function in Rat and Human Blood Vessels

Vitamin C Improves Attenuated Angiotensin II-Induced Endothelium-Dependent Vasodilation in Human Forearm Vessels

Significance of angiotensin II receptor blockers with high affinity to angiotensin II type 1 receptors for vascular protection in rats

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