Sosa-Canache B, Cierco M, Gutierrez C I, Israel A
Clinical Pharmacology Unit, School of Medicine, Universidad Centroccidental Lisandro Alvarado, Venezuela.
J Hum Hypertens. 2000 Apr;14 Suppl 1:S40-6. doi: 10.1038/sj.jhh.1000986.
Footshocks increases mean arterial pressure and heart rate. Systemic or intracerebroventricular (IVT) administration of losartan, a specific angiotensin AT1 receptor antagonist, not only inhibited the pressor response to footshocks but resulted in vasodepression. Peripheral or IVT administration of PD 123319, a specific angiotensin AT2 receptor antagonist, did not alter the haemodynamic response to footshocks. However, simultaneous blockade of angiotensin AT1 and AT2 receptors by combined systemic or central administration of losartan and PD 12319, eliminated the vasodepressor response to footshocks unmasked in losartan pretreated rats. Our data suggest that activation of peripheral or brain angiotensin AT2 receptor mediated the vasodepressor response to footshocks in the presence of angiotensin AT1 receptor antagonist. We studied the role of kinins and nitric oxide in the vasodepressor response observed after footshocks. The decrease in mean arterial pressure observed after footshocks in losartan treated rats was blunted by systemic or IVT administration of icatibant (HOE 140) or N(G)-nitro-L-arginine-methyl ester, indicating that peripheral or brain kinins and nitric oxide are involved in the hypotensor response to footshocks during angiotensin AT1 receptor blockade. Our results suggest a role for angiotensin AT2 receptor in the regulation of arterial blood pressure, possibly through the release of vasodilator autacoids such as bradykinins and nitric oxide.
足部电击会增加平均动脉压和心率。给予洛沙坦（一种特异性血管紧张素AT1受体拮抗剂）进行全身或脑室内（IVT）给药，不仅抑制了对足部电击的升压反应，还导致了血管舒张性低血压。给予PD 123319（一种特异性血管紧张素AT2受体拮抗剂）进行外周或IVT给药，并未改变对足部电击的血流动力学反应。然而，通过联合全身或中枢给予洛沙坦和PD 12319同时阻断血管紧张素AT1和AT2受体，消除了在洛沙坦预处理大鼠中所显现出的对足部电击的血管舒张性降压反应。我们的数据表明，在血管紧张素AT1受体拮抗剂存在的情况下，外周或脑内血管紧张素AT2受体的激活介导了对足部电击的血管舒张性降压反应。我们研究了激肽和一氧化氮在足部电击后观察到的血管舒张性降压反应中的作用。在洛沙坦处理的大鼠中，足部电击后观察到的平均动脉压降低被全身或IVT给予依替巴肽（HOE 140）或N(G)-硝基-L-精氨酸甲酯减弱，这表明外周或脑内激肽和一氧化氮参与了血管紧张素AT1受体阻断期间对足部电击的降压反应。我们的结果表明血管紧张素AT2受体在动脉血压调节中发挥作用，可能是通过释放血管舒张性自分泌物质如缓激肽和一氧化氮来实现的。
