Fontes M A, Silva L C, Campagnole-Santos M J, Khosla M C, Guertzenstein P G, Santos R A
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Brain Res. 1994 Nov 28;665(1):175-80. doi: 10.1016/0006-8993(94)91171-1.
In this study we determined which angiotensin receptors may mediate the cardiovascular effects elicited by angiotensin-(1-7) [Ang-(1-7)] in the rostral ventrolateral medulla (RVLM) and caudal pressor area (CPA) of the ventrolateral medulla (VLM) of anesthetized rats. Furthermore the role of endogenous angiotensins in these areas was also investigated. The pressor effect produced by unilateral microinjection of Ang-(1-7) into the RVLM or CPA was not modified by either the AT1 receptor antagonist, DuP 753 or by the AT2 receptor antagonist, CGP 42112A, but was completely blocked by the Ang-(1-7) selective antagonist, A-779. In contrast, the pressor effect produced by microinjection of angiotensin II (Ang II) was completely blocked by DuP 753 but was not changed by CGP 42112A or A-779. Bilateral microinjection of A-779 into the RVLM or CPA produced a significant fall in mean arterial pressure and heart rate. Microinjection of DuP 753 produced a pressor effect comparable to bilateral injection of vehicle. These results indicate that, although Ang II acts in the VLM through an AT1 receptor subtype, the cardiovascular effects produced by microinjection of Ang-(1-7) into the RVLM and CPA are mediated by a specific angiotensin receptor (AT5?). Furthermore, our data provide evidence that endogenous Ang-(1-7) participates at the VLM in the neural control of arterial blood pressure.
在本研究中,我们确定了在麻醉大鼠延髓腹外侧区头端腹外侧延髓(RVLM)和尾侧加压区(CPA)中,哪些血管紧张素受体可能介导血管紧张素-(1-7)[Ang-(1-7)]引发的心血管效应。此外,还研究了内源性血管紧张素在这些区域中的作用。向RVLM或CPA单侧微量注射Ang-(1-7)所产生的升压效应,既未被AT1受体拮抗剂杜普753(DuP 753)改变,也未被AT2受体拮抗剂CGP 42112A改变,但被Ang-(1-7)选择性拮抗剂A-779完全阻断。相比之下,微量注射血管紧张素II(Ang II)所产生的升压效应被杜普753完全阻断,但未被CGP 42112A或A-779改变。向RVLM或CPA双侧微量注射A-779可使平均动脉压和心率显著下降。微量注射杜普753所产生的升压效应与双侧注射溶媒相当。这些结果表明,尽管Ang II通过一种AT1受体亚型在延髓腹外侧区发挥作用,但向RVLM和CPA微量注射Ang-(1-7)所产生的心血管效应是由一种特定的血管紧张素受体(AT5?)介导的。此外,我们的数据提供了证据,表明内源性Ang-(1-7)参与延髓腹外侧区对动脉血压的神经控制。