The effects of isoflurane on adrenomedullin‐induced haemodynamic responses in pithed rats
The effects of isoflurane on adrenomedullin‐induced haemodynamic responses in pithed rats
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异氟烷对髓大鼠肾上腺髓质素诱导的血流动力学反应的影响
DOI：
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发表时间：
2008
影响因子：
3.6
通讯作者：
F. Goto
中科院分区：
文献类型：
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作者：
M. Kuroda;D. Yoshikawa;S. Koizuka;K. Nishikawa;S. Saito;F. Goto
背景和目的肾上腺髓质素是一种有效的血管扩张肽。肾上腺髓质素的作用机制与降钙素基因相关肽(CGRP)相似，是通过鸟苷3‘-三磷酸结合蛋白(G-Protein)偶联受体激活产生的。此前，我们曾报道七氟醚和异氟醚可抑制CGRP诱导的血流动力学反应。然而，挥发性麻醉剂对肾上腺髓质素诱导的血流动力学反应的影响尚不清楚。我们假设挥发性麻醉剂异氟醚抑制肾上腺髓质素诱导的血流动力学反应。我们研究了异氟烷对肾上腺髓质素诱导的大鼠血流动力学反应的影响，这使我们能够在不受中枢调节的循环反射干扰的情况下评估药物的直接心血管效应。方法雄性Wistar大鼠脊髓内插入不锈钢棒致伤。胸骨正中切开后，在升主动脉周围放置血流探头测量主动脉血流量。在持续输注去甲肾上腺素的情况下，平均动脉压和心输出量分别维持在约10 0毫米汞柱和50mLmin−1。吸入异氟醚(1%或2%)30min后，静脉注射肾上腺髓质素(1、3、10或30 mg·kg-1·−-1)。结果肾上腺髓质素引起一过性升高，随后平均动脉压和心输出量持续下降。异氟醚(2%)显著抑制平均动脉压的开始升高和后来的平均动脉压和全身血管阻力的下降。结论异氟醚抑制肾上腺髓质素诱导的大鼠血管扩张和正性肌力作用。异氟醚可能抑制肾上腺髓质素受体介导的反应，这是两种作用的共同途径。
Background and objectives Adrenomedullin is a potent vasodilatory peptide. The mechanisms of adrenomedullin‐induced responses are via guanine nucleotide guanosine 5′‐triphosphate‐binding protein (G‐protein)‐coupled receptor activation and are similar to those of calcitonin gene‐related peptide (CGRP). Previously, we reported that sevoflurane and isoflurane inhibit CGRP‐induced haemodynamic responses. The effects of volatile anaesthetics on adrenomedullin‐induced haemodynamic responses, however, are unclear. We hypothesized that the volatile anaesthetic isoflurane inhibits adrenomedullin‐induced haemodynamic responses. We studied the effects of isoflurane on adrenomedullin‐induced haemodynamic responses in pithed rats, which enables us to evaluate the direct cardiovascular effects of drugs without interference from centrally mediated circulatory reflexes. Methods Male Wistar rats were pithed by inserting a stainless‐steel rod into the spinal cord. Following median sternotomy, a flow probe was placed around the ascending aorta to measure aortic blood flow. Mean arterial pressure and cardiac output were maintained at approximately 100 mmHg and 50 mL min−1, respectively, with continuous infusion of norepinephrine. After 30 min inhalation of isoflurane (1%, or 2%) in oxygen, or only oxygen, adrenomedullin (1, 3, 10 or 30 &mgr;g kg−1) was administered intravenously. Results Adrenomedullin administration induced a transient increase followed by a persistent decrease in mean arterial pressure and cardiac output. Isoflurane (2%) significantly inhibited the initial increase in mean arterial pressure and the later decrease in mean arterial pressure and systemic vascular resistance. Conclusion Isoflurane inhibits adrenomedullin‐induced vasodilation and positive inotropic effect in pithed rats. Isoflurane might inhibit the adrenomedullin receptor‐mediated response, which is a common pathway for both actions.
肾上腺髓质素片段保留了大鼠肾上腺髓质素的全身血管抑制活性。
影响因子：
5
作者：
Lin,B;Gao,Y;Chang,JK;Heaton,J;Hyman,A;Lippton,H
通讯作者：
Lippton,H