Rabkin Simon W
University of British Columbia, 9th Floor 2775 Laurel St.,Vancouver, BC, Canada V5Z 1M9.
Neuropeptides. 2007 Dec;41(6):411-9. doi: 10.1016/j.npep.2007.09.003. Epub 2007 Nov 5.
The objectives of this study were to determine whether endogenous opioids are operative in modulating the CNS action of angiotensin II (ang II) on blood pressure and to determine whether this is mediated by endogenous mu or kappa opioid receptor agonists. The study design was: unanesthetized Wistar rats, 300-400g, previously instrumented with a cannula in the lateral cerebral ventricle and a catheter in the femoral artery, had ang II, 0.5microg, injected into the lateral cerebral ventricle (ICV). Groups were allocated to receive naloxone, a mu opioid receptor antagonist or MR 2266 a selective kappa opioid receptor antagonist prior to ang II. In other experiments in unanesthetized rats, baroreceptor reflex function was assessed by intravenous injection of phenylephrine or nitroprusside and the interaction of endogenous opioids and ang II ascertained with use of the mu or kappa opioid receptor antagonist .
Ang II significantly (p<0.05) increased systolic and diastolic blood pressure. The kappa opioid antagonist, MR 2266, 25microg/kg ICV, significantly (p<0.05) reduced and MR 2266, 50microg/kg ICV, completely prevented the increase in blood pressure produced by ang II. In contrast, the mu opioid receptor antagonist, naloxone, 50microg/kg, ICV, did not significantly attenuate the blood pressure responses to ang II. Ang II induced alteration in baroreceptor function. The effect of ang II on baroreceptor function was significantly antagonized by the kappa opioid receptor antagonist MR 2266. In conclusion, these data indicate that: (a) endogenous opioids modulate the pressor response to intracerebral ang II, (b) this effect is mediated mainly through endogenous kappa opioid agonists and kappa rather than mu opioid receptors, (c) alteration of baroreceptor sensitivity by ang II is modulated by endogenous kappa opioids.
本研究的目的是确定内源性阿片类物质是否在调节血管紧张素II（血管紧张素II）对血压的中枢神经系统作用中起作用，并确定这是否由内源性μ或κ阿片受体激动剂介导。研究设计如下：体重300 - 400克的未麻醉Wistar大鼠，先前已在侧脑室植入套管并在股动脉插入导管，将0.5微克血管紧张素II注入侧脑室（脑室内）。在注射血管紧张素II之前，将大鼠分组接受纳洛酮（一种μ阿片受体拮抗剂）或MR 2266（一种选择性κ阿片受体拮抗剂）。在未麻醉大鼠的其他实验中，通过静脉注射去氧肾上腺素或硝普钠评估压力感受器反射功能，并使用μ或κ阿片受体拮抗剂确定内源性阿片类物质与血管紧张素II的相互作用。
血管紧张素II显著（p<0.05）升高收缩压和舒张压。脑室内注射25微克/千克的κ阿片拮抗剂MR 2266显著（p<0.05）降低血压，而脑室内注射50微克/千克的MR 2266则完全阻止了血管紧张素II引起的血压升高。相比之下，脑室内注射50微克/千克的μ阿片受体拮抗剂纳洛酮并未显著减弱对血管紧张素II的血压反应。血管紧张素II诱导压力感受器功能改变。κ阿片受体拮抗剂MR 2266显著拮抗了血管紧张素II对压力感受器功能的影响。总之，这些数据表明：（a）内源性阿片类物质调节对脑内血管紧张素II的升压反应，（b）这种作用主要通过内源性κ阿片激动剂和κ而非μ阿片受体介导，（c）血管紧张素II对压力感受器敏感性的改变由内源性κ阿片类物质调节。
