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 and integrins may influence resistance artery structure and function and, therefore, peripheral resistance and blood pressure in spontaneously hypertensive rats (SHR). Methods and Results-Effects of age, angiotensin-converting enzyme inhibition (fosinopril, 10 to 30 mg/kg per day), and AT 1 -receptor antagonism (irbesartan, 50 mg/kg per day) on vascular structure, mechanics, and composition were assessed in SHR. Systolic
... in SHR. Systolic blood pressure was elevated in young SHR (130Ϯ2 mm Hg) compared with Wistar-Kyoto (WKY) rats (106Ϯ2 mm Hg). In adult SHR, the rise in systolic blood pressure (44Ϯ3 mm Hg) was blunted by fosinopril (18Ϯ1 mm Hg) and irbesartan (9Ϯ3 mm Hg). Lumen diameter of mesenteric resistance arteries was smaller and media/lumen ratio was greater in young and adult SHR versus WKY rats. Growth index was 24% in untreated adult SHR versus WKY rats; these values were Ϫ35% for fosinopril-treated and Ϫ29% for irbesartan-treated SHR versus untreated SHR. Isobaric wall stiffness was normal despite increased stiffness of wall components in adult SHR vessels. Irbesartan partially prevented stiffening of wall components in SHR. The collagen/elastin ratio was greater in adult SHR vessels (6.5Ϯ1.3) than in WKY (3.2Ϯ0.4) vessels. Expression of ␣ v ␤ 3 and ␣ 5 ␤ 1 integrins was increased in SHR aged 20 versus 6 weeks. Expression of ␣ 5 ␤ 1 integrins was lower in young SHR, and ␣ v ␤ 3 integrins were overexpressed in adult SHR versus WKY rats. Irbesartan and fosinopril attenuated differences in the collagen/elastin ratio and integrin expression. Conclusions-Wall components of mesenteric resistance arteries stiffen with age in SHR. Interrupting the renin-angiotensin system has normalizing effects on integrin expression and composition, stiffness, and growth of the arterial wall. Figure 4. Incremental elastic modulus-intraluminal pressure (top panels) and elastic modulus-media stress (bottom panels) curves in relaxed mesenteric arteries from 6-week-old (left) and 20-week-old (right) SHR and WKY rats (nՆ6). Error bars indicate SEM.