Attenuated cardioprotective response to bradykinin, but not classical ischaemic preconditioning, in DOCA-salt hypertensive left ventricular hypertrophy
Attenuated cardioprotective response to bradykinin, but not classical ischaemic preconditioning, in DOCA-salt hypertensive left ventricular hypertrophy
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DOI：
10.1016/j.phrs.2006.10.004
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发表时间：
2007-01-01
影响因子：
9.3
通讯作者：
Baxter, Gary F.
中科院分区：
文献类型：
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作者：
Ebrahim, Zaileen;Yellon, Derek M.;Baxter, Gary F.
高血压性左心室肥厚（LVH）经常与缺血性心脏病并存。虽然已知缺血预适应 (IPC) 可以防止 LVH 缺血再灌注损伤，但尚不清楚其他心脏保护措施是否有效。缓激肽是 IPC 中的一种关键自体介质，对正常心脏具有保护作用，但其预防 LVH 缺血再灌注损伤的能力尚不清楚。雄性大鼠用醋酸去氧皮质酮 (DOCA) 和盐饮用液治疗 4 周，诱发高血压 LVH。对心脏进行Langendorff灌注，进行35分钟冠状动脉闭塞和120分钟再灌注，并通过四唑染色测定梗塞面积(AN/RZ％)。评估了 IPC 2 x 5 分钟全缺血周期或 10 分钟缓激肽预处理的效果。 DOCA盐大鼠明显高血压，左心室/体重比比正常血压对照组高26%。正常血压心脏和 DOCA 盐心脏的基线冠状动脉流量和风险区/左心室比率相似，梗塞面积相似（AN/RZ 分别为 50.6 +/- 3.2% 和 47.0 +/- 3.1 %）。 IPC 对正常血压和 DOCA 盐心脏具有同等保护作用（AN/RZ 分别为 18.6 +/- 3.3% 和 18.4 +/- 2.3%，与相应对照相比，P < 0.01）。缓激肽 0.1、0.2 或 0.5 μM 预处理在正常血压心脏中产生浓度依赖性梗塞限制（缓激肽 0.5 μMAN/RZ，9.5 +/- 3.6%，与正常血压对照相比，P < 0.01），但在 DOCA 盐心脏中的效果减弱（缓激肽 0.5 μMAN/RZ，23.4） +/- 3.8%）。此外，在 DOCA 盐高血压心脏中，缺血前冠状血管舒张剂对缓激肽的反应被消除。我们得出的结论是，缓激肽的心脏保护作用在中度 LVH 中显着减弱，并且冠状血管扩张作用消失。高血压心脏对缓激肽敏感性降低的原因尚不清楚，但这些发现可能对预处理模拟干预措施在 LVH 中的应用有影响。 (c) 2006 Elsevier Ltd. 保留所有权利。
Hypertensive left ventricular hypertrophy (LVH) co-exists frequently with ischaemic heart disease. While ischaemic preconditioning (IPC) is known to protect against ischaemia-reperfusion injury in LVH, it is not known if other cardioprotective manoeuvres are effective. Bradykinin, a key autacoid mediator in IPC, is protective in normal hearts but its ability to protect against ischaemia-reperfusion injury in LVH is unknown. Hypertensive LVH was induced in male rats by 4 weeks treatment with deoxycorticosterone acetate (DOCA) and salt drinking fluid. Hearts were Langendorff perfused, subjected to 35 min coronary artery occlusion and 120 min reperfusion, and infarct size (AN/RZ %) was determined by tetrazolium staining. The effects of IPC with 2 x 5 min cycles of global ischaemia or 10 min pretreatment with bradykinin were assessed. DOCA-salt rats were markedly hypertensive and left ventricle/body weight ratio was 26% greater than in normotensive controls. Baseline coronary flow and risk zone/LV ratio were similar in normotensive hearts and DOCA-salt hearts, and infarct size was similar (AN/RZ 50.6 +/- 3.2% and 47.0 +/- 3.1 %, respectively). IPC was equally protective in normotensive and DOCA-salt hearts (AN/RZ 18.6 +/- 3.3% and 18.4 +/- 2.3%, respectively, P < 0.01 versus corresponding control). Bradykinin 0.1, 0.2 or 0.5 mu M pretreatment produced concentration-dependent infarct limitation in normotensive hearts (bradykinin 0.5 mu M AN/RZ, 9.5 +/- 3.6%, P < 0.01 versus normotensive control), but the effect in DOCA-salt hearts was attenuated (bradykinin 0.5 mu M AN/RZ, 23.4 +/- 3.8%). Further, the pre-ischaemic coronary vasodilator response to bradykinin was abrogated in DOCA-salt hypertensive hearts. We conclude that the cardioprotective action of bradykinin is markedly attenuated in moderate LVH and coronary vasodilator effect is lost. The reasons for reduced sensitivity to bradykinin in the hypertensive heart are unknown but these findings may have implications for the application of preconditioning-mimetic interventions in LVH. (c) 2006 Elsevier Ltd. All rights reserved.