Upregulated Expression of Rat Heart Intercellular Adhesion Molecule-1 in Angiotensin II

Intercellular adhesion molecule-1 (ICAM-1), part of an immunoglobulin-like superfamily of adhesion molecules, is involved in several cardiovascular diseases. We investigated whether in vivo angiotensin II (Ang II) increases ICAM-1 in rats. Sprague-Dawley rats were infused with vehicle or Ang II (750 mg z kg z d SC) for 7 days. The contribution of Ang II receptors to ICAM-1 expression was investigated with a nonpeptide Ang II type 1 (AT1) receptor antagonist losartan (30 mg z kg z d in drinking water). Systolic blood pressure was elevated in Ang II–treated animals compared with sham-treated controls, and losartan blocked this increase. Tumor necrosis factor (TNF)-a (5 mg/kg IP bolus), a prototype inducer of ICAM-1, was administered as a positive control for ICAM-1 expression. After treatment, hearts were frozen in liquid nitrogen; homogenates were subjected to SDS-PAGE and immunoblotted with an anti-rat ICAM-1 monoclonal antibody. We detected a predominantly high-molecular-weight band in homogenates from non–TNF-a–treated rats, which was enhanced by 8065% in TNF-a–treated rats. This band measured '200 kDa, which is the molecular weight of ICAM-1 in its native dimer form. The same band was detected in homogenates from sham and Ang II–treated rats, with the latter showing a 150610% increase in ICAM-1 versus sham controls. Immunoprecipitation of rat heart homogenates with anti-rat ICAM-1 antibody resulted in a dominant band of the same molecular weight as samples not treated with antibody. Losartan prevented enhanced expression of ICAM-1 in the presence of Ang II but had no effect on basal ICAM-1 expression. Phenylephrine, an a-agonist (3 mg z kg z d ), was infused for 1 week but had no effect on ICAM-1 expression, even though systolic blood pressure was elevated to the same level as in rats treated with Ang II. Thus, heart ICAM-1 expression is enhanced via AT1 receptor activation independent of hypertension. Ang II–induced ICAM-1 expression was time and dose dependent, with maximal expression occurring within 5 to 7 days at 100 to 750 mg/kg Ang II. Immunohistochemical staining demonstrated markedly increased ICAM-1 levels in the perivascular area in Ang II–infused rats. Monocyte/macrophage accumulation was significantly greater in Ang II–treated rat hearts than in sham-treated hearts (1061; P,0.001; n55). Thus during inflammation, overexpression of ICAM-1 may contribute to cardiovascular damage in diseases characterized by increased activity of the renin-angiotensin system. (Hypertension. 2001;37:58-65.)