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

Department of Internal Medicine, Faculty of Medicine, University of Messina, Italy

Maria Castaldo, MD

Department of Internal Medicine, Faculty of Medicine, University of Messina, Italy

Maurizio Cinquegrani, MD

Department of Internal Medicine, Faculty of Medicine, University of Messina, Italy

Michele Bonaiuto, MD

Department of Internal Medicine, Faculty of Medicine, University of Messina, Italy

Luisa Fontana, MD

Department of Internal Medicine, Faculty of Medicine, University of Messina, Italy

Salvatore Campo, PhD

Department of Internal Medicine, Faculty of Medicine, University of Messina, Italy

Giuseppe M. Campo, PhD

Institute of Pharmacology, Faculty of Medicine, University of Messina, Italy

Domenica Altavilla, PhD

Institute of Pharmacology, Faculty of Medicine, University of Messina, Italy

Antonino Saitta, MD

Department of Internal Medicine, Faculty of Medicine, University of Messina, Italy, asaitta{at}unime.it

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.

Angiology, Vol. 55, No. 2, 195-203 (2004)
DOI: 10.1177/000331970405500212


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