title: Effects of AT1 receptor antagonist losartan on sICAM-1 and TNF-alpha 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-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.
authors.affiliation: Department of Internal Medicine, University of Messina, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sardo
authors.forename: Maria
authors.initials: M
authors.lastname: Castaldo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cinquegrani
authors.forename: Michele
authors.initials: M
authors.lastname: Bonaiuto
authors.forename: Luisa
authors.initials: L
authors.lastname: Fontana
authors.forename: Salvatore
authors.initials: S
authors.lastname: Campo
authors.forename: Giuseppe M
authors.initials: GM
authors.lastname: Campo
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Antonino
authors.initials: A
authors.lastname: Saitta
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019808:Losartan