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

• Published in: Circulation (New York, N.Y.) N.Y.), 1999-11, Vol.100 (22), p.2267-2275
• Main Authors: INTENGAN, H. D, THIBAULT, G, LI, J.-S, SCHIFFRIN, E. L
• Format: Article
• Language: English
• Subjects: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Biphenyl Compounds - pharmacology; Blood and lymphatic vessels; Blood Pressure - drug effects; Body Weight - drug effects; Cardiology. Vascular system; Collagen - analysis; Elastin - analysis; Experimental diseases; Fosinopril - pharmacology; Hypertension - drug therapy; Hypertension - genetics; Hypertension - physiopathology; Hypertension - prevention & control; Integrins - metabolism; Irbesartan; Male; Medical sciences; Mesenteric Arteries - drug effects; Mesenteric Arteries - pathology; Oligopeptides - metabolism; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Tetrazoles - pharmacology; Vascular Resistance - drug effects
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.100.22.2267

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). 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 blood pressure was elevated in young SHR (130+/-2 mm Hg) compared with Wistar-Kyoto (WKY) rats (106+/-2 mm Hg). In adult SHR, the rise in systolic blood pressure (44+/-3 mm Hg) was blunted by fosinopril (18+/-1 mm Hg) and irbesartan (9+/-3 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 -35% for fosinopril-treated and -29% 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 (6.5+/-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 of alpha(5)beta(1) integrins was lower in young SHR, and alpha(v)beta(3) integrins were overexpressed in adult SHR versus WKY rats. Irbesartan and fosinopril attenuated differences in the collagen/elastin ratio and integrin expression. 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.