自发性高血压大鼠的阻力动脉力学、结构及细胞外成分：血管紧张素受体拮抗作用和转化酶抑制作用的影响

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

作者信息

Intengan H D, Thibault G, Li J S, Schiffrin E L

机构信息

MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.

出版信息

Circulation. 1999 Nov 30;100(22):2267-75. doi: 10.1161/01.cir.100.22.2267.

DOI:10.1161/01.cir.100.22.2267

PMID:10578002

Abstract

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 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.

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.

摘要

背景

胶原蛋白和整合素变化导致的血管力学改变可能影响阻力动脉的结构和功能，进而影响自发性高血压大鼠（SHR）的外周阻力和血压。

方法与结果

评估年龄、血管紧张素转换酶抑制（福辛普利，每天10至30毫克/千克）和AT(1)受体拮抗（厄贝沙坦，每天50毫克/千克）对SHR血管结构、力学和组成的影响。与Wistar-Kyoto（WKY）大鼠（106±2毫米汞柱）相比，年轻SHR的收缩压升高（130±2毫米汞柱）。在成年SHR中，福辛普利（18±1毫米汞柱）和厄贝沙坦（9±3毫米汞柱）使收缩压的升高（44±3毫米汞柱）减弱。与WKY大鼠相比，年轻和成年SHR的肠系膜阻力动脉管腔直径较小，中膜/管腔比值较大。未治疗的成年SHR与WKY大鼠相比，生长指数为24%；福辛普利治疗的SHR与未治疗的SHR相比，这些值为-35%，厄贝沙坦治疗的SHR与未治疗的SHR相比为-29%。尽管成年SHR血管壁成分的硬度增加，但等压壁硬度正常。厄贝沙坦部分阻止了SHR血管壁成分的硬化。成年SHR血管（6.5±1.3）中的胶原蛋白/弹性蛋白比值高于WKY血管（3.2±0.4）。与6周龄的SHR相比，20周龄的SHR中α(v)β(3)和α(5)β(1)整合素的表达增加。年轻SHR中α(5)β(1)整合素的表达较低，与WKY大鼠相比，成年SHR中α(v)β(3)整合素过度表达。厄贝沙坦和福辛普利减弱了胶原蛋白/弹性蛋白比值和整合素表达的差异。