Angiotensin II inhibition increases diuresis during acute sympathetic activation in intact and denervated kidneys in rats with chronic myocardial infarction
Angiotensin II inhibition increases diuresis during acute sympathetic activation in intact and denervated kidneys in rats with chronic myocardial infarction
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DOI：
10.1007/s00380-022-02110-2
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发表时间：
2022-06-11
影响因子：
1.5
通讯作者：
Saku, Keita
中科院分区：
文献类型：
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作者：
Kawada, Toru;Li, Meihua;Saku, Keita
我们检测了Wistar-Kyoto大鼠心肌梗死（MI）原发性急性交感神经激活（PASA）期间的尿排泄情况。冠状动脉结扎后7周行单侧肾去神经支配（RDN）。4 ~ 10 d后，在麻醉状态下进行急性实验（n = 8只大鼠）。将离体颈动脉窦压从60 mmHg逐步改变为180 mmHg，并检测动脉压（AP）与正常尿流量（nUF，尿流量按体重归一化）之间的关系。获得对照数据后，静脉给予血管紧张素II型1受体阻滞剂替米沙坦（2.5 mg/kg）。采用多元回归分析检验RDN、替米沙坦和心脏重量（双心室重量）对AP和nUF关系的影响。对于nUF与AP的斜率（nUF（斜率）），回归常数项为正（0.315 +/- 0.069 μ L中心点min（-1）中心点kg（-1）中心点mmHg(-1)），表明nUF随AP升高而升高。心脏重量对nUF（斜率）有负影响（P < 0.05），提示心肌梗死的严重程度与尿排泄障碍有关。替米沙坦增加nUF（斜率）0.358±0.080 μ L中心点min（-1）中心点kg（-1）中心点mmHg(-1) (P < 0.001)，而RDN对该参数无显著影响。结果表明，单侧RDN不能消除PASA时肾素-血管紧张素系统对尿排泄的影响。循环或局部产生的血管紧张素II，而不是持续的肾交感神经活动，在慢性心肌梗死大鼠PASA期间尿排泄障碍中起主导作用。
We examined urine excretion during primary acute sympathetic activation (PASA) in Wistar-Kyoto rats with myocardial infarction (MI). The rats underwent unilateral renal denervation (RDN) 7 weeks after coronary artery ligation. 4-10 days later, an acute experiment was performed under anesthetized conditions (n = 8 rats). Isolated carotid sinus pressure was changed stepwise from 60 to 180 mmHg, and the relationship between the arterial pressure (AP) and the normalized urine flow (nUF, urine flow normalized by the body weight) was examined. After obtaining the control data, an angiotensin II type 1 receptor blocker telmisartan (2.5 mg/kg) was intravenously administered. The effects of RDN, telmisartan, and heart weight (biventricular weight) on the relationship between AP and nUF were examined using multiple regression analyses. Regarding the slope of nUF versus AP (nUF(slope)), the constant term of the regression was positive (0.315 +/- 0.069 mu L center dot min(-1)center dot kg(-1)center dot mmHg(-1)), indicating that nUF increased with AP. The heart weight had a negative effect on nUF(slope) (P < 0.05), suggesting that the severity of MI was associated with the impairment of urine excretion. Telmisartan increased nUF(slope) by 0.358 +/- 0.080 mu L center dot min(-1)center dot kg(-1)center dot mmHg(-1) (P < 0.001), whereas RDN had no significant effect on this parameter. The results indicate that unilateral RDN was unable to abolish the effect of the renin-angiotensin system on urine excretion during PASA. Circulating or locally produced angiotensin II, rather than ongoing renal sympathetic nerve activity, played a dominant role in the impairment of urine excretion during PASA in rats with chronic MI.