Effects of AT1 receptor antagonist losartan on sICAM-1 and TNF-α levels in uncomplicated hypertensive patients

• Published in: Angiology Vol. 55; no. 2; pp. 195 - 203
• Main Authors: SARDO, Maria A, CASTALDO, Maria, CINQUEGRANI, Maurizio, BONAIUTO, Michele, FONTANA, Luisa, CAMPO, Salvatore, CAMPO, Giuseppe M, ALTAVILLA, Domenica, SAITTA, Antonino
• Format: Journal Article
• Language: English
• Published: Glen Head, NY Westminster 01-03-2004
• Subjects: Adult; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Humans; Hypertension - blood; Hypertension - drug therapy; Intercellular Adhesion Molecule-1 - blood; Losartan - therapeutic use; Male; Medical sciences; Middle Aged; Single-Blind Method; Tumor Necrosis Factor-alpha - metabolism; Human; Hypertension; Cardiovascular disease; Losartan; Tumor necrosis factor α; Cytokine
• ISSN: 0003-3197; 1940-1574
• DOI: 10.1177/000331970405500212

This study was designed to determine whether the levels of soluble intercellular adhesion molecule-1 (sICAM-1) and tumor necrosis factor-alpha (TNF-alpha) were elevated in subjects with uncomplicated hypertension who presented with no other risk factors or evidence of athero-sclerosis. 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-alpha 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-alpha 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-alpha levels, but no correlation in HT between the average diastolic and systolic blood pressure (clinic and ambulatory monitoring) and the sICAM-1 or TNF-alpha 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-alpha levels during losartan treatment was observed. These results show that patients with uncomplicated mild essential hypertension presented with high plasma ICAM-1 and TNF-alpha concentrations. Although all the patients were responsive to the antihypertensive treatment with losartan, their plasma concentrations of TNF-alpha 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.