Höcht Christian, Gironacci Mariela M, Mayer Marcos A, Schuman Mariano, Bertera Facundo M, Taira Carlos A
Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, (C1113AAD) Buenos Aires, Argentina.
Regul Pept. 2008 Feb 7;146(1-3):58-66. doi: 10.1016/j.regpep.2007.08.001. Epub 2007 Aug 15.
The role of anterior hypothalamic angiotensin-(1-7) (Ang-(1-7)) on blood pressure regulation was studied in sinoaortic denervated (SAD) rats. Since angiotensin-converting enzyme inhibitors increase endogenous levels of Ang-(1-7), we addressed the involvement of Ang-(1-7) in the hypotensive effect induced by captopril in SAD rats. Wistar rats 7 days after SAD or sham operation (SO) were anaesthetized and the carotid artery was cannulated for monitoring mean arterial pressure (MAP). A needle was inserted into the anterior hypothalamus for drug administration. Intrahypothalamic administration of Ang-(1-7) (5 pmol) was without effect in SO rats but reduced MAP in SAD rats by 15.5+/-3.2 mm Hg and this effect was blocked by 250 pmol [D-Ala(7)]-Ang-(1-7), a Mas receptor antagonist. Angiotensin II (Ang II) induced an increase in MAP in both groups being the effect greater in SAD rats (DeltaMAP=15.8+/-1.4 mm Hg) than in SO rats (DeltaMAP=9.6+/-1.0 mm Hg). Ang-(1-7) partially abolished the pressor response caused by Ang II in SAD rats. Whilst the captopril intrahypothalamic injection did not affect MAP in SO animals, it significantly reduced MAP in SAD rats (DeltaMAP=-13.3+/-1.9 mm Hg). Either [D-Ala(7)]-Ang-(1-7) or an anti-Ang-(1-7) polyclonal antibody partially blocked the MAP reduction caused by captopril. In conclusion, whilst Ang-(1-7) does not contribute to hypothalamic blood pressure regulation in SO normotensive animals, in SAD rats the heptapeptide induces a reduction of blood pressure mediated by Mas receptor activation. Although Ang-(1-7) is not formed in enough amount in the AHA of SAD animals to exert cardiovascular effects in normal conditions, our results suggest that enhancement of hypothalamic Ang-(1-7) levels by administration of captopril is partially involved in the hypotensive effect of the ACE inhibitor.
研究了下丘脑前部血管紧张素 -（1 - 7）（Ang -（1 - 7））在去窦主动脉神经支配（SAD）大鼠血压调节中的作用。由于血管紧张素转换酶抑制剂会增加内源性Ang -（1 - 7）水平，我们探讨了Ang -（1 - 7）在卡托普利诱导的SAD大鼠低血压效应中的作用。对SAD术后7天或假手术（SO）的Wistar大鼠进行麻醉，将颈动脉插管以监测平均动脉压（MAP）。将一根针插入下丘脑前部用于给药。下丘脑内注射Ang -（1 - 7）（5 pmol）对SO大鼠无影响，但使SAD大鼠的MAP降低了15.5±3.2 mmHg，且该效应被250 pmol的Mas受体拮抗剂[D - Ala（7）]-Ang -（1 - 7）阻断。血管紧张素II（Ang II）使两组大鼠的MAP均升高，SAD大鼠的效应（ΔMAP = 15.8±1.4 mmHg）大于SO大鼠（ΔMAP = 9.6±1.0 mmHg）。Ang -（1 - 7）部分消除了Ang II在SAD大鼠中引起的升压反应。虽然下丘脑内注射卡托普利对SO动物的MAP无影响，但它显著降低了SAD大鼠的MAP（ΔMAP = - 13.3±1.9 mmHg）。[D - Ala（7）]-Ang -（1 - 7）或抗Ang -（1 - 7）多克隆抗体均可部分阻断卡托普利引起的MAP降低。总之，在SO正常血压动物中，Ang -（1 - 7）对下丘脑血压调节无作用，但在SAD大鼠中，该七肽通过Mas受体激活诱导血压降低。虽然在SAD动物的下丘脑前部，Ang -（1 - 7）的生成量不足以在正常情况下发挥心血管效应，但我们的结果表明，通过给予卡托普利提高下丘脑Ang -（1 - 7）水平部分参与了ACE抑制剂的降压作用。
