Antiinflammatory Effects of Angiotensin II Subtype 1 Receptor Blockade in Hypertensive Patients With Microinflammation

Abstract

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.

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

“…Serum levels of hsCRP, an anti-inflammatory marker, were significantly decreased by olmesartan, but not amlodipine, an observation consistent with a previous study. 25 As additional confirmation of the anti-inflammatory property of olmesartan, we measured urine monocyte chemoattractant protein-1 levels finding that, though not statistically significant, olmesartan tended to decrease urine monocyte chemoattractant protein-1 levels. Regarding EC-SOD, an antioxidative property of the vasculature, neither pre-nor post-EC-SOD levels, or the resulting heparin-releasable EC-SOD levels were changed by either treatment.…”

“…The present study demonstrated that olmesartan significantly reduced serum hsCRP levels as previously reported. 25,[45][46][47] However, the changes in hsCRP levels were not associated with those in FMD. As in the case of microalbuminuria, as RAS inhibition produces pleiotropic effects, there may not be a simple one-to-one correlation between serum hsCRP levels and endothelial function either.…”

The effect of aliskiren on urinary cytokine/chemokine responses to clamped hyperglycaemia in type 1 diabetes

“…We have recently demonstrated that inflammatory urine biomarkers also increase in response to acute clamped hyperglycaemia; however, the role of the RAAS in mediating this response and the reversibility of this phenomenon was unknown. We hypothesised that blockade of the RAAS would mitigate the effect of clamped hyperglycaemia on urinary cytokines/chemokines [37][38][39][40].…”

Comparative efficacy and safety of aliskiren and irbesartan in patients with hypertension and metabolic syndrome

“…22 Assuming a CV of 30%, it was determined that 100 completed patients (50 per group) would provide 90% power to detect a 20% difference between patient groups, whereas a CV of 50% would provide 50% power to detect the same change.…”