Background-Experimental studies revealed proinflammatory properties of angiotensin II. We evaluated antiinflammatory effects of the angiotensin II subtype 1 receptor antagonist olmesartan medoxomil alone and in cotherapy with the HMG-CoA reductase inhibitor pravastatin in patients with essential hypertension and microinflammation. Methods and Results-We measured a panel of vascular inflammation markers, including high-sensitivity C-reactive protein, and lipid levels during 12 weeks of therapy with olmesartan (nϭ100) or placebo (nϭ99) in a prospective double-blind multicenter study. Pravastatin was added to the double-blind therapy at week 6 in both treatment arms. Blood pressure control was achieved with addition of hydrochlorothiazide. Olmesartan treatment had already significantly reduced serum levels of high-sensitivity C-reactive protein (Ϫ15.1%; PϽ0.05), high-sensitivity tumor necrosis factor-␣ (Ϫ8.9%; PϽ0.02), interleukin-6 (Ϫ14.0%; PϽ0.05), and monocyte chemotactic protein-1 (Ϫ6.5%; PϽ0.01) after 6 weeks of therapy, whereas placebo treatment (ie, blood pressure reduction) had no major effect on inflammation markers. After 12 weeks of therapy, high-sensitivity C-reactive protein (Ϫ21.1%; PϽ0.02), highsensitivity tumor necrosis factor-␣ (Ϫ13.6%; PϽ0.01), and interleukin-6 (Ϫ18.0%; PϽ0.01) decreased further with olmesartan and pravastatin cotherapy, but treatment with pravastatin alone (ie, cotherapy with placebo) did not significantly alter inflammation markers. In contrast, addition of pravastatin led to a significant (PϽ0.001) reduction in LDL cholesterol serum concentrations in the olmesartan and placebo treatment groups (Ϫ15.1% and Ϫ12.1%, respectively). Conclusions-Angiotensin II receptor blockade significantly reduces vascular microinflammation in patients with essential hypertension by as early as week 6 of therapy. This antiinflammatory action of angiotensin II receptor antagonists may contribute to their beneficial cardiovascular effects.

Our findings suggest reduced vagal and increased sympathetic tone during mental challenge in salt-sensitive subjects. Altered autonomic nervous system function may contribute to later development of hypertension in salt-sensitive individuals.

Salt sensitivity (SS) represents a risk factor for essential hypertension, which has been related to enhanced cardiovascular stress reactivity possibly mediated by increased noradrenergic susceptibility. We investigated biophysiological responses to mental stress in salt-sensitive (ss) and salt-resistant (sr) subjects, hypothesizing lower heart rate variability (HRV) and higher cortisol in the ss. A total of 48 healthy normotensive Caucasian men (age 25.6±2.6, body mass index 22.9±2.3) were phenotyped for SS (defined as significant drop in mean arterial pressure43 mm Hg under the low-salt diet) by a 2-week high-versus low-salt diet. Subjects underwent a standardized mental stress task with continuous cardiovascular monitoring before, during and after the test (Finapres; Ohmeda, Louisville, CO, USA). Blood samples were drawn to examine cortisol and catecholamines before, after and 20 min after stress. The task elicited significant increases of systolic blood pressure (SBP), diastolic BP (DBP) and heart rate (HR) and a significant decrease of HRV (all time effects Po0.0001). The ss subjects showed lower norepinephrine (NE) and higher cortisol, indicated by significant group effects (P ¼ 0.009 and 0.025, respectively). HR increased and HRV decreased more in the ss under the stress, shown by significant time by group interactions (P ¼ 0.045 and 0.003, respectively). The observation of a more pronounced HR rise coupled with a greater decrease of HRV in healthy ss men under the influence of brief mental stress confirms their enhanced physiological stress reactivity. The lower peripheral NE may represent an effort to compensate for increased noradrenergic receptor sensitivity. The enhanced cortisol levels are backed by recent genetic findings on HSD11B2 polymorphisms and may promote hypertension.

An increased responsiveness of the blood pressure to mental stress and an increased level of irritation are associated with salt sensitivity in normotensive subjects. These findings are in line with the hypothesis that psychophysiological traits play a role in the development of salt-sensitive hypertension.

Individuals whose mean arterial blood pressure is depending on oral salt intake are considered salt-sensitive and are at risk of developing essential hypertension. This study investigates the role of salt-sensitivity with respect to systolic blood pressure reactions under standardized mental stress. Forty-three healthy young males, previously characterized as salt-sensitive (n=16) or salt-resistant (n=27) by a dietary regimen, were subjected to multimodal physiological measurement during a computerized stress test and underwent comprehensive psychometrical testing. The most important predictors for systolic blood pressure reactions to stress were the degree of salt-sensitivity, body mass index and psychological characteristics like anxiety. The highest correlations with the degree of salt-sensitivity were found for the parameters age, systolic blood pressure reaction under stress, high frequency band of heart rate variability and two psychological variables. The concept of salt-sensitivity is a novel biological component that might contribute to reactivity research in subjects at high risk for essential hypertension.