Resistance artery mechanics, structure, and extracellular components in spontaneously hypertensive rats - Effects of angiotensin receptor antagonism and converting enzyme inhibition

Background-Altered vascular mechanics resulting from changes in collagen an d integrins may influence resistance artery structure and function and, the refore, peripheral resistance and blood pressure in spontaneously hypertens ive rats (SHR). Methods ann Results-Effects of age, angiotensin-converting enzyme inhibitio n (fosinopril, 10 to 30 mg/kg per day), and AT(1)-receptor antagonism (irbe sartan, 50 mg/kg per day) on vascular structure, mechanics, and composition were assessed in SHR. Systolic blood pressure was elevated in young SHR (1 30+/-2 mm Hg) compared with Wistar-Kyoto (WKY) rats (106+/-2 mm Hg). In adu lt SHR, the rise in systolic blood pressure (44+/-3 mm Hg) was blunted by f osinopril (18+/-1 mm Hg) and irbesartan (9+/-3 mm Hg). Lumen diameter of me senteric resistance arteries was smaller and media/lumen ratio was greater in young and adult SHR versus WKY rats. Growth index was 24% in untreated a dult SHR versus WKY rats; these values were -35% for fosinopril-treated and -29% for irbesartan-treated SHR versus untreated SHR, Isobaric wall stiffn ess was normal despite increased stiffness of wall components in adult SHR vessels. Irbesartan partially prevented stiffening of wall components in SH R. The collagen/elastin ratio was greater in adult SHR vessels (6.5+/-1.3) than in WKY (3.2+/-0.4) vessels. Expression of alpha(v)beta(3) and alpha(5) beta(1) integrins was increased in SHR aged 20 versus 6 weeks. Expression o f alpha(5)beta(1) integrins was lower in young SHR, and alpha(v)beta(3) int egrins were overexpressed in adult SHR versus WKY rats. Irbesartan and fosi nopril attenuated differences in the collagen/elastin ratio and integrin ex pression. Conclusions-Wall components of mesenteric resistance arteries stiffen with age in SHR. Interrupting the renin-angiotensin system has normalizing effec ts on integrin expression and composition, stiffness, and growth of the art erial wall.