DifferentialMechanisms of Ang (1-7)-Mediated Vasodepressor Effect in Adult and Aged Candesartan-Treated Rats
DifferentialMechanisms of Ang (1-7)-Mediated Vasodepressor Effect in Adult and Aged Candesartan-Treated Rats
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DOI：
10.1155/2012/192567
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发表时间：
2012-01-01
影响因子：
1.9
通讯作者：
Jones, E. S.
中科院分区：
文献类型：
--
作者：
Bosnyak, S.;Widdop, R. E.;Jones, E. S.
血管紧张素（1-7）（Ang（1-7））通过血管紧张素Ⅱ受体（AT 2 R）对WKY大鼠和自发性高血压大鼠（SHR）产生血管舒张作用。然而，血管AT（2）R在衰老中的作用尚不清楚。因此，我们研究了衰老对Ang（1-7）介导的血管降压效应和血管紧张素受体定位的影响。测量清醒成人的血压（类似于17周）和年龄（类似于19个月）血压正常的大鼠，在4天的方案中以随机方式接受药物组合：（i）单独的Ang（1-7），（ii）单独的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PD 123319。还通过免疫荧光法在成年和老年WKY大鼠的主动脉切片中评估受体定位。Ang（1-7）降低成年正常血压大鼠的血压（类似于15 mmHg），尽管这种作用依赖于坎地沙坦的背景剂量。阻断AT（2）R可逆转这种降压作用。在老年大鼠中，Ang（1-7）的降压作用是明显的，但现在被AT（2）R阻断或MasR阻断所抑制。同时，AT（2）R、MasR和ACE 2免疫反应性在老年动物的主动脉切片中显著升高。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。而在成年WKY中，Ang（1-7）的作用仅通过刺激AT（2）R介导，随着年龄的增长，Ang（1-7）的血管抑制作用涉及AT（2）R和MasR。
Angiotensin (1-7) (Ang (1-7)) causes vasodilator effects in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) via angiotensin type 2 receptors (AT2R). 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 (similar to 17 weeks) and aged (similar to 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 (similar to 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.