Acute angiotensin-converting enzyme inhibition evokes bradykinin-induced sympathetic activation in diabetic rats.
Acute angiotensin-converting enzyme inhibition evokes bradykinin-induced sympathetic activation in diabetic rats.
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急性血管紧张素转换酶抑制会引起糖尿病大鼠缓激肽诱导的交感神经激活。
DOI：
10.1152/ajpregu.00509.2007
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Rossi,NoreenF
中科院分区：
文献类型：
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作者：
Augustyniak,RobertA;Maliszewska-Scislo,Maria;Chen,Haiping;Fallucca,John;Rossi,NoreenF
我们之前的研究表明，急性静脉注射血管紧张素转换酶（ACE）抑制剂依那普利在糖尿病大鼠中引起了一种不依赖于压力反射的交感神经兴奋作用，而血管紧张素受体单独阻断不会发生这种作用。由于ACE抑制也阻断了缓激素的降解，我们试图确定缓激素是否介导了这种作用。实验在清醒的雄性Sprague-Dawley大鼠中进行，长期测量链脲佐菌素（55 mg/kg静脉注射，糖尿病，n= 11）或柠檬酸盐（正常，n= 10） 2周后的平均动脉压（MAP）、心率（HR）和肾交感神经活动（RSNA）。依那普利（2.5 mg/kg iv）降低了正常大鼠的MAP(- 15±3 mmHg)，而糖尿病大鼠的反应较小（- 4±1 mmHg）。尽管对依那普利有不同的降压药反应，但两组之间HR（+44±8 vs +26±7 bpm）和RSNA（+90±21 vs +71±8%基线）的增加相似（两者的P均≥0.22）。缓激素b2受体拮抗剂ho140预处理（10 μg/kg灌胃后再灌胃0.8·μg - 1kg·min - 1）可减轻依那普利对正常大鼠MAP的降低，但对糖尿病大鼠无影响。此外，正常组的HR和RSNA反应较小（HR: +13±8 bpm； RSNA: +32±13%基线），而糖尿病组（HR: - 4±5 bpm； RSNA: - 5±9%基线；与preenalapril值相比P< 0.05）则完全消失。此外，与正常大鼠相比，缓激肽（20 μg/kg iv）在糖尿病大鼠中引起的交感神经兴奋作用更大、更持久，并在依那普利治疗后进一步增强。我们的结论是，增强的缓激肽信号介导依那普利在糖尿病大鼠的压力反射非依赖性交感神经兴奋作用。
We have previously shown that acute intravenous injection of the angiotensin-converting enzyme (ACE) inhibitor enalapril in diabetic rats evokes a baroreflex-independent sympathoexcitatory effect that does not occur with angiotensin receptor blockade alone. As ACE inhibition also blocks bradykinin degradation, we sought to determine whether bradykinin mediated this effect. Experiments were performed in conscious male Sprague-Dawley rats, chronically instrumented to measure mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), 2 wk after streptozotocin (55 mg/kg iv, diabetic,n= 11) or citrate vehicle (normal,n= 10). Enalapril (2.5 mg/kg iv) decreased MAP in normal rats (−15 ± 3 mmHg), while a smaller response (−4 ± 1 mmHg) occurred in diabetic rats. Despite these different depressor responses to enalapril, HR (+44 ± 8 vs. +26 ± 7 bpm) and RSNA (+90 ± 21 vs +71 ± 8% baseline) increased similarly between the groups (P≥ 0.22 for both). Pretreatment with the bradykinin B2receptor antagonist Hoe 140 (10 μg/kg bolus followed by 0.8·μg−1kg·min−1infusion) attenuated the decrease in MAP observed with enalapril in normal rats but had no effect in diabetic rats. Moreover, the normal group had smaller HR and RSNA responses (HR: +13 ± 8 bpm; RSNA: +32 ± 13% baseline) that were abolished in the diabetic group (HR: −4 ± 5 bpm; RSNA: −5 ± 9% baseline;P< 0.05 vs. preenalapril values). Additionally, bradykinin (20 μg/kg iv) evoked a larger, more prolonged sympathoexcitatory effect in diabetic compared with normal rats that was further potentiated after treatment with enalapril. We conclude that enhanced bradykinin signaling mediates the baroreflex-independent sympathoexcitatory effect of enalapril in diabetic rats.