(Hypertension. 1999;33:366-372.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Role of AT2 Receptors in Angiotensin II–Stimulated Contraction of Small Mesenteric Arteries in Young SHR
From the Medical Research Council Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal and Université de Montréal, Montreal, Quebec, Canada.
Correspondence to Rhian M. Touyz, MD, PhD, Clinical Research Institute of Montreal, 110 Pine Ave W, Montreal (Quebec), Canada H2W 1R7. E-mail touyz{at}ircm.umontreal.ca
Abstract—This study assesses the
receptor subtype (AT1 and AT2) through which
angiotensin II (Ang II) mediates contraction in small
arteries of young and adult spontaneously hypertensive rats (SHR).
Segments of third-order mesenteric arteries (
200 µm in lumen
diameter) were mounted in a pressurized system. Systolic blood
pressure and media:lumen ratio of small arteries were significantly
greater (P<0.001) in young SHR and adult SHR than in
age-matched Wistar-Kyoto rats (WKY). Ang II–induced contractile
effects were significantly increased (P<0.05) in young
SHR compared with age-matched WKY. AT1 blockade with
losartan, and combined AT1 and AT2
blockade with losartan and PD123319, abolished Ang
II–stimulated contraction in young and adult rats. AT2
blockade (PD123319) significantly reduced (P<0.01) Ang
II–elicited contraction in young SHR but had no effect in WKY or adult
SHR, indicating that AT2 receptors may contribute to Ang
II–induced contraction in young SHR. To determine the Ang receptor
status in rat mesenteric vessels, AT1 and AT2
receptor mRNA expression was determined by reverse
transcription–polymerase chain reaction. AT1 and
AT2 receptor protein expression were detected by Western
blot analysis. AT1 receptor mRNA was equally
expressed in age-matched rats, but expression was significantly lower
in young rats compared with adult rats. AT2 receptor mRNA
was weakly expressed in WKY and adult SHR. In vessels from young SHR,
AT2 receptor mRNA expression was significantly increased
compared with the other groups. AT1 receptor protein was
equally expressed in adult rats of both strains but was undetectable in
young rats. AT2 receptor protein was only detectable in
young rats, with the magnitude of expression greater in SHR than WKY.
In conclusion, Ang II–stimulated contractile responses are augmented
in vessels from young SHR. These effects are reduced by selective
AT2 blockade and abolished by AT1 blockade,
indicating that both Ang receptor subtypes are involved in contraction
in young SHR. In WKY and adult SHR, losartan, but not PD123319,
inhibited Ang II–induced contraction, indicating the exclusive
involvement of AT1 receptors. Thus, in SHR, in the phase of
developing hypertension, enhanced Ang II–stimulated vascular
contraction may be associated with changes in Ang II receptor status,
as evidenced pharmacologically and by increased vascular
AT2 receptor mRNA and protein expression.
Key Words: resistance • arteries • hypertension • receptors, angiotensin • vasoconstriction • PD123319 • losartan
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