Authors: Miloradović, Zoran; Jovović, Đurđica; Mihailović-Stanojević, Nevena; Milanović, Jelica G.r.u.j.i..; Milanović, Slađan

Source: Canadian Journal of Physiology and Pharmacology, Volume 86, Number 4, April 2008 , pp. 210-214(5)

Publisher: NRC Research Press

Abstract:

Recently, it has been reported that losartan, an angiotensin II receptor (ATR) antagonist, depresses the angiotensin II-induced production of superoxide radicals. Also, in spontaneously hypertensive rats (SHR) endothelial dysfunction is associated with decreased nitric oxide (NO) synthesis. In this study, we examined the effects of long-term ATR blockade and <span class="smallcap">l</span>-arginine supplementation on the haemodynamic parameters, glomerular filtration, and oxidative status in SHR. Adult male SHR were treated with losartan (10 mg/kg) and with the NO donor <span class="smallcap">l</span>-arginine (2 g/kg) for 4 weeks. The animals were divided into the following experimental groups: control (n = 7), <span class="smallcap">l</span>-arginine (n = 7), losartan (n = 7), and <span class="smallcap">l</span>-arginine + losartan (n = 7). Mean arterial pressure (MAP), regional blood flow, urea clearance, and activity of superoxide dismutase (SOD) were measured at the end of treatment. MAP was significantly reduced in the losartan group compared with the control group (133.3 ± 7.3 vs. 161.5 ± 14.5 mm Hg). Aortic blood flow was significantly higher and aortic vascular resistance was significantly lower in all treated groups than in the control. Urea clearance rose significantly in the <span class="smallcap">l</span>-arginine + losartan group compared with control (393.27 ± 37.58 vs. 218.68 ± 42.03 μL·min^-1·100 g^-1),<span class="smallcap"></span> as did the activity of SOD (1668.97 ± 244.57 vs. 1083.18 ± 169.96 U/g Hb). Our results suggest that the antihypertensive effect of losartan and <span class="smallcap">l</span>-arginine in SHR is not primarily mediated by increased SOD activity. Also, combined treatment with ATR blockade and <span class="smallcap">l</span>-arginine supplementation has a beneficial effect on renal function that is, at least in part, mediated by increased SOD activity in SHR.

Récemment, on a rapporté que le losartan, un antagoniste des récepteurs de l'angiotensine-II (ATR), diminue la production de radicaux superoxyde induite par l'angiotensine-II. De plus, chez les rats spontanément hypertendus (RSH), la dysfonction endothéliale est associée à une diminution de la synthèse du monoxyde d'azote (NO). Nous avons examiné les effets d'un blocage prolongé des ATR et d'une supplémentation en <span class="smallcap">l</span>-arginine sur les paramètres hémodynamiques, la filtration glomérulaire et l'état oxydatif chez les RSH. Nous avons traité des RSH mâles adultes avec du losartan (10 mg/kg) et avec le donneur de NO, <span class="smallcap">l</span>-arginine (2 g/kg), durant quatre semaines. Nous avons réparti les animaux dans les quatre groupes expérimentaux suivants : témoin (n = 7), <span class="smallcap">l</span>-arginine (n = 7), losartan (n = 7) et <span class="smallcap">l</span>-arginine + losartan (n = 7). Nous avons mesuré la pression artérielle moyenne (PAM), le débit sanguin régional, la clairance de l'urée et l'activité de la superoxyde dismutase (SOD) à la fin du traitement. La PAM a diminué de façon significative chez le groupe losartan par rapport à celle du groupe témoin (133,3 ± 7,3 vs. 161,5 ± 14,5 mm Hg). Le débit sanguin aortique a augmenté significativement et la résistance vasculaire aortique a diminué de manière significative chez tous les groupes traités par comparaison à ce qui a été observé chez le groupe témoin. La clairance de l'urée a augmenté de manière significative chez le groupe arginine+losartan par rapport à celle du groupe témoin (393,27 ± 37,58 vs. 218,68 ± 42,3 ±42,3 μL·min^-1·100 g^-1). L'activité de la SOD a augmenté de façon significative chez le groupe <span class="smallcap">l</span>-arginine + losartan comparativement à celle du groupe témoin (1668,97 ± 244,57 vs. 1083,18 ± 169,96 U/g Hb). Nos résultats donnent à penser que, chez les RSH, l'effet antihypertenseur du losartan et de la <span class="smallcap">l</span>-arginine n'est pas véhiculé par une augmentation de l'activité SOD essentiellement.

Document Type: Research article

Publication date: 2008-04-01

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