(Circulation. 1999;100:2267.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Resistance Artery Mechanics, Structure, and Extracellular Components in Spontaneously Hypertensive Rats
Effects of Angiotensin Receptor Antagonism and Converting Enzyme Inhibition
From the MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.
Correspondence to Ernesto L. Schiffrin, MD, PhD, FRCPC, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, Quebec, Canada H2W 1R7. E-mail schiffe{at}IRCM.qc.ca
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 AT1-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
vß3 and 5ß1
integrins was increased in SHR aged 20 versus 6 weeks. Expression of
5ß1 integrins was lower in young SHR, and
vß3 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.
Key Words: arteries • mechanics • remodeling • collagen • cell adhesion molecules
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