Bosnyak S, Widdop R E, Denton K M, Jones E S
Departments of Pharmacology, Monash University, Clayton, VIC 3800, Australia.
Int J Hypertens. 2012;2012:192567. doi: 10.1155/2012/192567. Epub 2011 Nov 30.
Angiotensin (1-7) (Ang (1-7)) causes vasodilator effects in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) via angiotensin type 2 receptors (AT(2)R). However, the role of vascular AT(2)R in aging is not known. Therefore, we examined the effect of aging on Ang (1-7)-mediated vasodepressor effects and vascular angiotensin receptor localization in aging. Blood pressure was measured in conscious adult (17 weeks) and aged (19 months) normotensive rats that received drug combinations in a randomised fashion over a 4-day protocol: (i) Ang (1-7) alone, (ii) AT(1)R antagonist, candesartan, alone, (iii) Ang (1-7) and candesartan, or (iv) Ang-(1-7), candesartan, and the AT(2)R antagonist, PD123319. In a separate group of animals, the specific MasR antagonist, A779, was administered in place of PD123319. Receptor localisation was also assessed in aortic sections from adult and aged WKY rats by immunofluorescence. Ang (1-7) reduced blood pressure (~15 mmHg) in adult normotensive rats although this effect was dependant on the background dose of candesartan. This depressor effect was reversed by AT(2)R blockade. In aged rats, the depressor effect of Ang (1-7) was evident but was now inhibited by either AT(2)R blockade or MasR blockade. At the same time, AT(2)R, MasR, and ACE2 immunoreactivity was markedly elevated in aortic sections from aged animals. These results indicate that the Ang (1-7)-mediated depressor effect was preserved in aged animals. Whereas Ang (1-7) effects were mediated exclusively via stimulation of AT(2)R in adult WKY, with aging the vasodepressor effect of Ang (1-7) involved both AT(2)R and MasR.
血管紧张素（1-7）（Ang（1-7））通过2型血管紧张素受体（AT（2）R）在Wistar-Kyoto（WKY）大鼠和自发性高血压大鼠（SHR）中产生血管舒张作用。然而，血管AT（2）R在衰老过程中的作用尚不清楚。因此，我们研究了衰老对Ang（1-7）介导的血管降压作用和衰老过程中血管紧张素受体定位的影响。在清醒的成年（约17周）和老年（约19个月）正常血压大鼠中测量血压，这些大鼠在4天的实验方案中以随机方式接受药物组合：（i）单独使用Ang（1-7），（ii）单独使用AT（1）R拮抗剂坎地沙坦，（iii）Ang（1-7）和坎地沙坦，或（iv）Ang-（1-7）、坎地沙坦和AT（2）R拮抗剂PD123319。在另一组动物中，给予特异性MasR拮抗剂A779代替PD123319。还通过免疫荧光评估成年和老年WKY大鼠主动脉切片中的受体定位。Ang（1-7）降低成年正常血压大鼠的血压（约15 mmHg），尽管这种作用取决于坎地沙坦的背景剂量。这种降压作用被AT（2）R阻断所逆转。在老年大鼠中，Ang（1-7）的降压作用明显，但现在被AT（2）R阻断或MasR阻断所抑制。同时，老年动物主动脉切片中AT（2）R、MasR和ACE2的免疫反应性明显升高。这些结果表明，Ang（1-7）介导的降压作用在老年动物中得以保留。在成年WKY中，Ang（1-7）的作用仅通过刺激AT（2）R介导，随着衰老，Ang（1-7）的血管舒张降压作用涉及AT（2）R和MasR两者。
