Angiotensin-(1-7) blockade attenuates captopril- or hydralazine-induced cardiovascular protection in spontaneously hypertensive rats treated with NG-nitro-L-arginine methyl ester.
Angiotensin-(1-7) blockade attenuates captopril- or hydralazine-induced cardiovascular protection in spontaneously hypertensive rats treated with NG-nitro-L-arginine methyl ester.
复制标题
DOI：
10.1097/fjc.0b013e31821324b6
复制
发表时间：
2011-05
影响因子：
3
通讯作者：
Diz DI
中科院分区：
文献类型：
--
作者：
Benter IF;Yousif MH;Al-Saleh FM;Raghupathy R;Chappell MC;Diz DI
我们评估了血管紧张素-（1-7）[Ang-（1-7）]对自发性高血压大鼠（SHR）中卡托普利诱导的心血管保护作用的贡献，SHR长期接受一氧化氮合成抑制剂L-NAME（SHR-L）治疗。给予L-NAME（80 mg/L）3周使平均动脉压（MAP）从196 ± 6 mmHg增加到229 ± 3 mmHg（p<0.05）。用Ang-（1-7）拮抗剂[D-Ala 7]-血管紧张素-（1-7）（A779; 744 μg/kg/天ip）治疗SHR-L进一步使MAP升高至253 ± 6 mmHg（p<0.05 vs. SHR-L或SHR）。此外，A779治疗减弱了卡托普利（300 mg/L饮用水）或肼苯哒嗪（1.5 mg/kg/天ip）引起的MAP和蛋白尿减少。在离体灌注心脏中，全脑缺血后左心室功能的恢复通过卡托普利或肼苯哒嗪治疗增强，并且通过A779加重。Ang-（1-7）拮抗剂减弱了卡托普利和肼苯哒嗪对心功能的有益作用。在灌注和再灌注期间，用卡托普利急性灌注的离体SHR-L心脏从全脑缺血中的恢复也得到改善。急性给药A779降低了卡托普利改善缺血后恢复的有益作用。我们的结论是，在一氧化氮可用性降低期间，内源性Ang-（1-7）发挥保护作用，有效地缓冲血压和肾损伤的增加，以及从心肌缺血中恢复。此外，在严重高血压和终末器官损伤模型中，Ang-（1-7）有助于卡托普利和肼苯哒嗪的血压降低和组织保护作用。
We assessed the contribution of angiotensin-(1-7) [Ang-(1-7)] to captopril-induced cardiovascular protection in spontaneously hypertensive rats (SHR) chronically treated with the nitric oxide synthesis inhibitor L-NAME (SHR-L). L-NAME (80 mg/L) administration for three weeks increased mean arterial pressure (MAP) from 196 ± 6 mmHg to 229 ± 3 mmHg (p<0.05). Treatment of SHR-L with Ang-(1-7) antagonist, [D-Ala7]-Angiotensin-(1-7) (A779; 744 μg/kg/day ip) further elevated MAP to 253 ± 6 mmHg (p<0.05 vs. SHR-L or SHR). Moreover, A779 treatment attenuated the reduction in MAP and proteinuria by either captopril (300 mg/L in drinking water) or hydralazine (1.5 mg/kg/day ip). In isolated perfused hearts, the recovery of left ventricular function from global ischemia was enhanced by captopril or hydralazine treatment, and was exacerbated with A779. The Ang-(1-7) antagonist attenuated the beneficial effects of captopril and hydralazine on cardiac function. Recovery from global ischemia was also improved in isolated SHR-L hearts acutely perfused with captopril during both the perfusion and reperfusion periods. The acute administration of A779 reduced the beneficial actions of captopril to improve recovery following ischemia. We conclude that during periods of reduced nitric oxide availability, endogenous Ang-(1-7) plays a protective role to effectively buffer the increase in blood pressure and renal injury, as well as the recovery from cardiac ischemia. Moreover, Ang-(1-7) contributes to the blood pressure lowering and tissue protective actions of captopril and hydralazine in a model of severe hypertension and end-organ damage.