Hypertension and Vascular Remodeling Depend on the Immunological Background in Mice

Abstract

Hypertension is associated with inward remodeling of small arteries. We propose that vascular remodeling relates to inflammation of the vessel wall and depends on the immunological background. We determined cardiovascular parameters and inflammatory responses in mice, which received NG‐nitro‐L‐arginine methyl ester (L‐NAME) to induce hypertension. Two strains of mice with a genetically different immune background were used: C57BL/6 mice, a T‐helper 1 dominant phenotype (n=14); and BALB/c mice, a T‐helper 2 dominant phenotype (n=40), additionally treated or not with TCR peptides to promote a T‐helper 1 response. After 4 weeks, L‐NAME treatment induced a significant increase in mean arterial blood pressure in C57BL/6 mice (+53%), but not in BALB/c mice (+8%; NS), unless treated with TCR peptides (+13%). Arteries from C57BL/6 mice showed an increase in the wall‐to‐lumen ratio, which was absent in BALB/c mice, unless treated with TCR peptides. In both strains, a complex inflammatory response was found after 3 days of L‐NAME treatment, which had returned to baseline values after 4 weeks. The inflammatory response was similar in the two strains, except for the leukocyte marker CD11b, which showed an increased expression in C57BL/6 only. Confocal microscopy confirmed the presence of CD11b+/CD68− leukocytes in the vessel wall. These data show that vascular remodeling and hypertension are strain dependent. Mice with a T‐helper 1 phenotype are highly susceptible to the development of vascular remodeling and hypertension.