Fontes M A, Martins Pinge M C, Naves V, Campagnole-Santos M J, Lopes O U, Khosla M C, Santos R A
Departamento de Fisiologia e Biofisica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Brain Res. 1997 Mar 7;750(1-2):305-10. doi: 10.1016/s0006-8993(96)01476-x.
In this study we determined the cardiovascular effects produced by microinjection of angiotensin peptides [Angiotensin-(1-7) and Angiotensin II] and angiotensin antagonists (losartan, L-158,809, CGP 42112A. Sar1-Thr8-Ang II, A-779) into the rostral ventrolateral medulla of freely moving rats. Microinjection of angiotensins (12.5-50 pmol) produced pressor responses associated to variable changes in heart rate, usually tachycardia. Unexpectedly, microinjection of both AT1 and AT2 ligands produced pressor effects at doses that did not change blood pressure in anesthetized rats. Conversely, microinjection of Sar1-Thr8-Ang II and the selective Ang-(1-7) antagonist, A-779, produced a small but significant decrease in MAP an HR. These findings suggest that angiotensins can influence the tonic activity of vasomotor neurons at the RVLM. As previously observed in anesthetized rats, our results further suggest a role for endogenous Ang-(1-7) at the RVLM. The pressor activity of the ligands for AT1 and AT2 angiotensin receptor subtypes at the RVLM, remains to be clarified.
在本研究中,我们测定了向自由活动大鼠的延髓头端腹外侧区微量注射血管紧张素肽[血管紧张素-(1-7)和血管紧张素II]及血管紧张素拮抗剂(氯沙坦、L-158,809、CGP 42112A、Sar1-Thr8-血管紧张素II、A-779)所产生的心血管效应。微量注射血管紧张素(12.5 - 50皮摩尔)会产生与心率变化相关的升压反应,通常为心动过速。出乎意料的是,微量注射AT1和AT2配体在未改变麻醉大鼠血压的剂量下却产生了升压效应。相反,微量注射Sar1-Thr8-血管紧张素II和选择性血管紧张素-(1-7)拮抗剂A-779会使平均动脉压和心率出现小幅但显著的下降。这些发现表明血管紧张素可影响延髓头端腹外侧区血管运动神经元的紧张性活动。正如之前在麻醉大鼠中所观察到的那样,我们的结果进一步表明内源性血管紧张素-(1-7)在延髓头端腹外侧区发挥作用。血管紧张素受体亚型AT1和AT2的配体在延髓头端腹外侧区的升压活性仍有待阐明。