Losartan enhances arterial compliance and reduces exercise BP in metabolic syndrome patients

The metabolic syndrome nearly triples risk for CVD. Patients with the metabolic syndrome have stiffer arteries that may contribute to their excessive pressor responses to exercise. In addition to basal BP, arterial stiffness and exercise systolic (S)BP have emerged as CVD predictors. Data suggest that AT1 antagonists (ATA) may be especially useful for improving arterial compliance and reducing exercise SBP even more than baseline SBP. 12 patients with the metabolic syndrome (age 45±2, BP 142±2/92±1 mmHg, waist girth 110±3 cm, triglycerides 186±23, HDL-C 44±2 mg/dL) were studied off all medications, while on modest Na+ restriction (∼100 mmol/d). Patients were randomized to receive LosartanÒ 100 mg QD or placebo for 3 weeks then crossed over to the complement for 3 weeks. After an overnight fast, hemodynamic variables at rest were obtained with the HDI PulseWaveÒ. BP was measured during a standard 6-minute ETT. Losartan lowered baseline SBP from 142±3 to 131±3 mmHg at rest (p<0.001) and 192±6 to 169±5 mmHg during exercise (p<0.001). Losartan lowered BP more during exercise than at rest (−23±3 vs −11±2 mmHg, p<0.05). Losartan improved large artery elasticity at rest from 13.6±0.7 to 16.2±1.1 ml/mmHg (p<0.01). Serum lipids and biomarkers of oxidative stress (F2-isoprostanes, TBARS) were unchanged. Losartan reduces the SBP response to exercise, perhaps by enhancing arterial compliance independently of effects on lipids and biomarkers of oxidative stress. The positive effects of ATA on CVD in high-risk patients may be mediated in part by beneficial effects on arterial compliance and SBP reactivity.