Background: Angiotensin II type 1 (AT1) receptor blocker therapy prevented or retarded the progression of coronary heart disease. The mechanisms of this benefit may relate to the ability of AT1 receptor blockers to reduce inflammation. Methods: We administered placebo or candesartan 16 mg daily during 2 months to 45 patients with mild to moderate hypertension. This study was randomized, double-blind, placebo-controlled, crossover in design. Results: Candasartan therapy significantly lowered both systolic and diastolic blood pressure and improved flow-mediated dilation and decreased plasma malondialdehyde levels. Compared with placebo, candesartan therapy significantly lowered plasma hsCRP levels relative to baseline measurements from 1.10 to 0.70 mg/l (P=0.024) and sCD40L levels by 30±11% (P<0.001) and TNF-α by 10±4% (P=0.026) and MCP-1 by 9±3% (P=0.003). There were significant inverse correlations between body mass index and baseline plasma adiponectin levels (r=-0.480, p=0.009). There were significant correlations between baseline adiponectin levels and baseline HDL-cholesterol levels (r=0.499, p<0.001). Compared with placebo, candesartan therapy significantly increased plasma levels of adiponectin by 15±4% (P=0.012). There were significant correlations between percent changes in adiponectin levels and percent changes in HDL-cholesterol (r=0.309, p=0.041). We investigated whether candesartan-induced changes in inflammation markers were mediated by reduction of systolic or diastolic blood pressure following candesartan. There were no significant correlations between these changes and reduction of systolic blood pressure (-0.254≤r≤0.171) and between these changes and reduction of diastolic blood pressure (-0.271≤r≤0.158). Furthermore, despite an experimental study showing a mechanism for the regulation of adiponectin by TNF-α, we observed no significant correlations between adiponectin and TNF-α levels. Conclusions: Candesartan therapy significantly improved the percent flow-mediated dilator response to hyperemia and reduced levels of oxidant stress and inflammation markers and increased adiponectin levels in hypertensive patients.
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