Effects of AT1 Receptor Antagonist Losartan on sICAM-1 and TNF-a Levels in Uncomplicated Hypertensive Patients

Abstract

This study was designed to determine whether the levels of soluble intercellular adhesion molecule-1 (sICAM-1) and tumor necrosis factor-a (TNF-a) were elevated in subjects with uncomplicated hypertension who presented with no other risk factors or evidence of atherosclerosis. The effects of administration of an angiotensin type-1 antagonist (losartan) on the serum concentrations of these molecules were also examined. Twenty hypertensive (HT) subjects (12 men and 8 women, mean age 49.1 ±7.2 years) without other risk factors or cardiovascular disease received placebo for 4 weeks. The patients were then treated with losartan (50 mg/day) for 24 weeks. After 4, 12, and 24 weeks of losartan treatment, sICAM-1 and TNF-a levels were measured. The same parameters were measured in 20 normotensive control subjects (C), matched for sex and age. HT had sICAM-1 and TNF-a basal values higher than C (respectively 351.7 ±97.4 vs 201.6 ±32.3 ng/mL, p<0.001 and 31.8 ±2.4 vs 15.3 ±2.2 pg/mL, p<0.001). There was a positive correlation between sICAM-1 and TNF-a levels, but no correlation in HT between the average diastolic and systolic blood pressure (clinic and ambulatory monitoring) and the sICAM-1 or TNF-a levels was observed. Losartan treatment caused a significant decrease of sICAM-1 levels at the end of the first month of treatment (300.2 ±64.4 ng/mL, p<0.05), but the values reverted to the basal levels at the following time points. No variation of TNF-a levels during losartan treatment was observed. These results show that patients with uncomplicated mild essential hypertension presented with high plasma ICAM-1 and TNF-a concentrations. Although all the patients were responsive to the antihypertensive treatment with losartan, their plasma concentrations of TNF-a were not modified, and sICAM-1 concentrations decreased only for a short period of time. This suggests that in uncomplicated hypertension other factors besides the blood pressure modulate the endothelial inflammation.

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