High blood pressure (HBP) has been associated with elevated C-reactive protein (CRP), a marker of chronic mild inflammation. However, the association between HBP and other inflammatory markers, particularly interleukin 6 (IL-6) and tumour necrosis alpha (TNF-a), has not been evaluated in well-controlled studies. We examined the cross-sectional relationship between IL-6, TNF-a, and CRP and HBP in a random sample of 196 healthy subjects. All markers were measured in duplicate with high-sensitivity ELISA tests. Three blood pressure (BP) measurments were averaged for the analysis, and subjects with systolic BP X140 and/or diastolic BP X90 mmHg were considered hypertensive. Log binomial regression was used to estimate multivariate-adjusted prevalence ratios (PR) of HBP. Of the subjects, 40% (79) were hypertensive (mean age: 44 years; range 30-64). After adjustment for age, sex, body mass index, family history of HBP, and the level of the other inflammatory markers, subjects in the second (PR: 3.10, P ¼ 0.003), third (PR: 2.32; P ¼ 0.031), and fourth quartiles (PR: 2.30; P ¼ 0.036) of IL-6 were more than twice as likely to be hypertensive than those in the first quartile. Corresponding PR estimates for TNF-a levels were 1.41 (P ¼ 0.014) for the second; 1.59 (P ¼ 0.001) for the third; and 1.61 (P ¼ 0.025) for the fourth quartile. The CRP-HBP association was not statistically significant. Our results suggest that TNF-a and IL-6 could be independent risk factors for HBP in apparently healthy subjects. Nevertheless, the temporal relationship between elevated inflammation markers and HBP should be ascertained in prospective cohort studies.

Preeclampsia is a pregnancy-specific disorder characterised by hypertension and proteinuria occurring after the 20th week of gestation. Delivery of the placenta results in resolution of the condition, implicating the placenta as a central culprit in the pathogenesis of preeclampsia. In preeclampsia, an inadequate placental trophoblast invasion of the maternal uterine spiral arteries results in poor placental perfusion, leading to placental ischaemia. This could result in release of factors into the maternal circulation that cause widespread activation or dysfunction of the maternal endothelium. Factors in the maternal circulation might induce oxidative stress and/or elicit an inflammatory response in the maternal endothelium, resulting in the altered expression of several genes involved in the regulation of vascular tone. This review addresses the potential circulating factors and the molecular mechanisms involved in the alteration of vascular function that occurs in preeclampsia.

Removal of ovarian hormones increased LV remodeling in the aged rat, which could be attenuated by estrogen replacement. Moreover, regulation of Ang II receptor expression could be a mechanism by which estrogen may modulate heart remodeling.

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Objective-Angiotensin II (AII) has been shown to increase endothelial NAD(P)H oxidase activity, which is a source of superoxide anion that in turn may induce the formation of peroxynitrite. Estrogen (E 2 ) has been reported to have vascular protective effects. In this study, we hypothesized that E 2 reduces the AII-induced expression of NAD(P)H oxidase and peroxynitrite in endothelial cells. Methods and Results-Endothelial cells were cultured and stimulated with AII in the absence or presence of E 2 . Western blots were used to assess nitric oxide synthase (NOS) and NAD(P)H oxidase expression. Immunofluorescence of nitrotyrosine provided evidence of peroxynitrite formation. Our data indicate that AII increased the expression of endothelial NOS, inducible NOS, and NAD(P)H oxidase in a dose-dependent manner, which was attenuated by incubation with either E 2 , superoxide dismutase, or the AII type 1 receptor (AT 1 R) inhibitor candesartan. Estrogen as well as superoxide dismutase also inhibited AII-induced AT 1 R expression and nitrotyrosine staining. The effects of E 2 on the AII responses were not inhibited by the E 2 receptor antagonist ICI-182,780. Conclusions-AII stimulation of endothelial cells increases expression of NAD(P)H oxidase and NOS, which maycontribute to oxidative stress, as evidenced by peroxynitrite formation. E 2 inhibits these AII effects, possibly through reduced AT 1 R expression. Key Words: estrogen Ⅲ angiotensin Ⅲ oxidative stress Ⅲ endothelium Ⅲ peroxynitrite C ardiovascular disease is the leading cause of death worldwide to date, and hypertension and atherosclerosis are significant risk factors. An important regulator of these risk factors is the vasoactive peptide angiotensin II (AII). Although AII is a potent vasoconstrictor by itself, it has other important functions in the vasculature. For instance, AII is known to enhance free radical production, such as superoxide anion, through activation of NAD(P)H oxidase. 1,2 This action of AII to promote oxidative stress may be contributing to vascular endothelial dysfunction. Indeed, oxidative stress along with endothelial cell dysfunction is associated with hypertension 3 and atherosclerosis, 4,5 which are precipitating factors for ischemic heart disease. See coverNAD(P)H oxidase is composed of 4 subunits: two cytosolic components (p47 phox and p67 phox ) and two membranebound components (p22 phox and gp91 phox ); these subunits are associated with a small G-protein, Rac. 6 NAD(P)H oxidase, originally found in leukocytes, is present in other cell types. Indeed, recent work has demonstrated that NAD(P)H oxidase represents the most significant source of superoxide anion in endothelial cells. 7 Interestingly, AII is known to increase expression and activation of endothelial NAD(P)H oxidase. 8,9 Nitric oxide (NO) is a free radical, and it is a potent vasodilator produced from NO synthase (NOS). AII stimulates release of NO to modulate the vasoconstrictor actions of AII in the short term. 10 However, AII infusion for 7 days in rats caused increas...