Role of AT 2 Receptors in Angiotensin II–Stimulated Contraction of Small Mesenteric Arteries in Young SHR

Abstract

Abstract —This study assesses the receptor subtype (AT 1 and AT 2 ) 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. AT 1 blockade with losartan, and combined AT 1 and AT 2 blockade 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 adult SHR, indicating that AT 2 receptors may contribute to Ang II–induced contraction in young SHR. To determine the Ang receptor status in rat mesenteric vessels, AT 1 and AT 2 receptor mRNA expression was determined by reverse transcription–polymerase chain reaction. AT 1 and AT 2 receptor protein expression were detected by Western blot analysis. AT 1 receptor mRNA was equally expressed in age-matched rats, but expression was significantly lower in young rats compared with adult rats. AT 2 receptor mRNA was weakly expressed in WKY and adult SHR. In vessels from young SHR, AT 2 receptor mRNA expression was significantly increased compared with the other groups. AT 1 receptor protein was equally expressed in adult rats of both strains but was undetectable in young rats. AT 2 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 AT 2 blockade and abolished by AT 1 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 AT 1 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 AT 2 receptor mRNA and protein expression.