Mechanisms of Ischemia Reperfusion Injury in Microperfused Afferent Arterioles.

微灌注传入小动脉缺血再灌注损伤的机制。

• 批准号: 07670800
• 负责人: HANO Takuzo
• 金额: $ 1.47万
• 依托单位: Wakayama Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670800/
• 关键词: rabbit; reperfusion injury; glomerulus; afferent arterioles; endothelium; calcium antagonist

Ischemia reperfusion injury is one of the most important pathophysiological phenomena, which occurs in shock, transplants and other ischemic disease. This study was carried out to determine the mechanisms of ischemia reperfusion injury in microvessels.After 15-minute ischemia and 30-minute reperfusion, rabbit afferent arterioles (Af-Art) with the glomerulus intact were microdissected from the superficial cortex of the rabbit kidney and perfused in vitro at 60mmHg. Vasoconstrictor action of norepinephirine (NE) and vasodilator action of acetylcholin (Ach) or nicardipine (Nic) were examined. Af-Art were examined with an electron microscope.Nic 1mg/kg/min was addminstrated intravenously 15 minute before the occulusion of renal artery. Then same protocol was repeated again.The ischemia reperfusion significantly attenuated the dilation induced by 10^<-5>M Ach 4.7% (n=5) VS 5.4% in controls (n=5)}. However, the response to 5x10^<-7>M NE remained unchanged 4.6% (n=4) VS 6.5% in controls (n=8)}, as did the dilation induced by 10^<-7>M Nic 6.5% (n=7) VS 6.5% in controls (n=7)}. Slight damages were observed in the endothelial cells on electron microscopy. There was no damage to Af-Arts after 20 minutes ischemia only, either functionally or histologically. Pretreatment of Nic could reverse endothelial damage by ischemia reperfusion injury.We conclude that short period of the ischema reparfusion could induce functional and histological damage to Af-Art. The endothelial cells of microvessels are more susceptible to ischemia reperfusion than smooth muscle cells. Calcium antagonist improve the endothelial damage by ischemia reperfusion injury via calcium channel dependent mechanisms.

缺血再灌注损伤是最重要的病理生理现象之一，发生在休克，移植和其他缺血性疾病中。进行了这项研究以确定微血管中缺血再灌注损伤的机制。在15分钟的缺血和30分钟的再灌注后，从兔子和兔子肾肾表面的浅表皮质中微调，将兔子传入小动脉（af-Arterioles（af-Art）与肾小球完整。在60mmHg的体外灌注。检查了乙酰胆碱（ACH）或尼古丁（NIC）的去甲肾上腺素（NE）和血管扩张剂的血管收缩作用。用电子显微镜检查Af-Art。在肾动脉碰撞前15分钟，将1mg/kg/min的NIC 1mg/kg/min添加。然后再次重复相同的方案。缺血再灌注显着减弱了10^<-5> m ACh 4.7％（n = 5）和对照组5.4％的扩张（n = 5）}。但是，对5x10^<-7> m ne的响应保持不变的4.6％（n = 4）对照组（n = 8）}，而10^<-7> M NIC诱导的扩张也是6.5％，而对照组为6.5％（n = 8）}。 （n = 7）对照组（n = 7）}的6.5％。在电子显微镜上的内皮细胞中观察到轻微的损害。仅在功能或组织学上，缺血20分钟后，AF-ARTS没有损害。 NIC的预处理可能会通过缺血再灌注损伤逆转内皮损害。我们得出的结论是，缺血的短期可以诱导AF-ART的功能性和组织学损害。微血管的内皮细胞比平滑肌细胞更容易受到缺血再灌注。钙拮抗剂通过钙通道依赖机制通过缺血再灌注损伤改善内皮损伤。

项目成果

Ken Kasamatsu, Yoshinari Nakamura, Mituaid Katsuragi, Miido Arita, Shigehiro Tomimoto, Hano Takuzo, Ichiro Nishio.: "The Effect of Angiotensin II AT1 blockade on Renal Sympathetic Nerve Activity and Baroreflex Function in Conscious Rats with Heart Failure

Ken Kasamatsu、Yoshinari Nakamura、Mituaid Katsuragi、Miido Arita、Shigehiro Tomimoto、Hano Takuzo、Ichiro Nishio.：“血管紧张素 II AT1 阻断对心力衰竭清醒大鼠肾交感神经活动和压力反射功能的影响

Takuzo Hano: "The production of nitrogen oxide by cultured vascular endothelial and smooth muscle cells from spontaneously hypertensive and Wista Kyoto rats" Japanese Heart Journal. 37 (8). 582 (1996)

Takuzo Hano：“自发性高血压大鼠和 Wista 京都大鼠培养的血管内皮细胞和平滑肌细胞产生一氧化氮”，《日本心脏杂志》。

Masahiko Shiotani: "Angiotensin II (3-8) Has Vasodilatopry Action Mediated by Nitric Oxide on Isolated Microperfused Renal Afferent Arterioles in the Rabbit." Circulation. 94・8. I693-I694 (1996)

Masahiko Shiotani：“血管紧张素 II (3-8) 对兔循环中的孤立微灌注肾传入小动脉具有一氧化氮介导的血管舒张作用”(1996)。

Takuzo Hano: "The production of nitrogen oxide by cultured vascular endothelial and smooth muscle cells from spontaneously hypertensive and Wistar Kyoto rat" Japanese Heart Journal. 37(4). 582- (1996)

Takuzo Hano：“自发性高血压和 Wistar 京都大鼠培养的血管内皮细胞和平滑肌细胞产生氮氧化物”《日本心脏杂志》。

Akira Baba: "Prolonged time courses of intracellular calcium transient and contraction-relaxation in isolated left ventricular myocytes from spontaneously hypertensive rats" Heart Vessel. Suppl 9. 147-149 (1995)

Akira Baba：“自发性高血压大鼠离体左心室肌细胞中细胞内钙瞬变和收缩松弛的延长时间过程”心脏血管。