We investigated the role of angiotensin II in vascular and circulating inflammatory markers in spontaneously hypertensive rats (SHR). IL-1beta, IL-6, and TNF-alpha aortic mRNA expression and plasma levels were measured in adult SHR untreated or treated with the angiotensin II receptor antagonist candesartan (2 mg.kg(-1).day(-1)) or antihypertensive triple therapy (TT; in mg.kg(-1).day(-1): 20 hydralazine + 7 type 1 hydrochlorothiazide + 0.15 reserpine) for 10 wk. Likewise, aortic expression of NF-kappaB p50 subunit precursor p105 and its inhibitor (IkappaB) were measured. Age-matched Wistar-Kyoto rats (WKY) served as normotensive reference. High blood pressure levels were associated with increased (P < 0.05) aortic mRNA expression of IL-1beta, IL-6, and TNF-alpha. Hypertension was also accompanied by increased IL-1beta and IL-6 plasma levels. No differences were observed in circulating TNF-alpha levels between SHR and WKY. SHR presented elevated aortic mRNA expression of the transcription factor NF-kappaB and reduction in its inhibitor, IkappaB. Candesartan decreased (P < 0.05) blood pressure levels, aortic mRNA expression of IL-1beta, IL-6, and TNF-alpha, and (P < 0.05) IL-1beta and IL-6 plasma concentration. However, although arterial pressure decrease was comparable for the treatments, TT only partially reduced the increments in inflammatory markers. In fact, candesartan-treated rats showed significantly lower levels of circulating and vascular inflammatory markers than TT-treated animals. The treatments increased IkappaB mRNA expression similarly. However, only candesartan reduced NF-kappaB mRNA expression. In summary, 1) SHR presented a vascular inflammatory process; 2) angiotensin II, and increased hemodynamic forces associated with hypertension, seems to be involved in stimulation of inflammatory mediators through NF-kappaB system activation; and 3) reduction of inflammatory mediators produced by candesartan in SHR could be partially due to both downregulation of NF-kappaB and upregulation of IkappaB.

The study investigated whether the amelioration of endothelial dysfunction by candesartan (2 mg.kg-1.day-1; 10 wk) in spontaneously hypertensive rats (SHR) was associated with modification of hepatic redox system. Systolic arterial pressure (SAP) was higher (P < 0.05) in SHR than in Wistar-Kyoto rats (WKY) and was reduced (P < 0.05) by candesartan in both strains. Acetylcholine (ACh) relaxations were smaller (P < 0.05) and contractions induced by ACh + NG-nitro-l-arginine methyl ester (l-NAME) were greater (P < 0.05) in SHR than in WKY. Treatment with candesartan enhanced (P < 0.05) ACh relaxations in SHR and reduced (P < 0.05) ACh + l-NAME contractions in both strains. Expression of aortic endothelial nitric oxide synthase (eNOS) mRNA was similar in WKY and SHR, and candesartan increased (P < 0.05) it in both strains. Aortic mRNA expression of the subunit p22phox of NAD(P)H oxidase was higher (P < 0.05) in SHR than in WKY. Treatment with candesartan reduced (P < 0.05) p22phox expression only in SHR. Malonyl dialdehyde (MDA) levels were higher (P < 0.05), and the ratio reduced/oxidized glutathione (GSH/GSSG) as well as glutathione peroxidase activity (GPx) were lower (P < 0.05) in liver homogenates from SHR than from WKY. Candesartan reduced (P < 0.05) MDA and increased (P < 0.05) GSH/GSSG ratio without affecting GPx. Vessel, lumen, and media areas were bigger (P < 0.05) in SHR than in WKY. Candesartan treatment reduced (P < 0.05) media area in SHR without affecting vessel or lumen area. The results suggest that hypertension is not only associated with elevation of vascular superoxide anions but with alterations of the hepatic redox system, where ANG II is clearly involved. The results further support the key role of ANG II via AT1 receptors for the functional and structural vascular alterations produced by hypertension.

SUMMARY BackgroundThe prevalence of gastro-oesophageal reflux disease (GERD), has not been characterized in Spain.

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