Rm. Touyz et al., Role of AT(2) receptors in angiotensin II-stimulated contraction of small mesenteric arteries in young SHR, HYPERTENSIO, 33(1), 1999, pp. 366-372
Citations number
45
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
This study assesses the receptor subtype (AT(1) and AT(2)) through which an
giotensin II (Ang II) mediates contraction in small arteries of young and a
dult spontaneously hypertensive rats (SI-IR). Segments of third-order mesen
teric arteries (approximate to 200 mu m in lumen diameter) were mounted in
a pressurized system. Systolic blood pressure and media:lumen ratio of smal
l 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 eff
ects were significantly increased (P<0.05) in young SHR compared with age-m
atched WKY. AT(1) blockade with losartan, and combined AT(1) and AT(2) bloc
kade with losartan and PD123319, abolished Ang II-stimulated contraction in
young and adult rats. AT(2) blockade (PD123319) significantly reduced (P<0
.01) Ang II-elicited contraction in young SHR but had no effect in WKY or a
dult SHR, indicating that AT(2) receptors may contribute to Ang II-induced
contraction in young SHR. To determine the Ang receptor status in rat mesen
teric vessels, AT(1) and AT(2) receptor mRNA expression was determined by r
everse transcription-polymerase chain reaction. AT(1) and AT(2) receptor pr
otein expression were detected by Western blot analysis. AT(1) receptor mRN
A was equally expressed in age-matched rats, but expression was significant
ly lower in young rats compared with adult rats. AT(2) receptor mRNA was we
akly expressed in WKY and adult SHR. In vessels from young SHR, AT(2) recep
tor mRNA expression was significantly increased compared with the ether gro
ups. AT(1) receptor protein was equally expressed in adult rats of both str
ains but was undetectable in young rats. AT(2) receptor protein was only de
tectable in young rats, with the magnitude of expression greater in SHR tha
n WKY. In conclusion, Ang II-stimulated contractile responses are augmented
in vessels from young SHR. These effects are reduced by selective AT(2) bl
ockade and abolished by AT(1) blockade, indicating that both Ang receptor s
ubtypes are involved in contraction in young SHR. In WKY and adult SHR, los
artan, but not PD123319, inhibited Ang II-induced contraction, indicating t
he exclusive involvement of AT(1) receptors. Thus, in SHR, in the phase of
developing hypertension, enhanced Ang II-stimulated vascular contraction ma
y be associated with changes in Ang II receptor status, as evidenced pharma
cologically and by increased vascular AT(2) receptor mRNA and protein expre
ssion.