Gardiner Sheila M, March Julie E, Kemp Philip A, Davenport Anthony P, Wiley Katherine E, Bennett Terence
Centre for Integrated Systems Biology and Medicine School of Biomedical Sciences, University of Nottingham NG7 2UH. UK.
J Pharmacol Exp Ther. 2005 Jan;312(1):53-60. doi: 10.1124/jpet.104.075259. Epub 2004 Aug 24.
In conscious male Sprague-Dawley rats, we compared regional hemodynamic actions of the selective corticotropin-releasing factor type 2 (CRF(2)) receptor ligands human and mouse urocortin 2 (hUCN2 and mUCN2, respectively) with those of CRF. Bolus i.v. doses of 3 and 30 pmol kg(-1) hUCN2, mUCN2, or CRF had no significant hemodynamic actions, but at doses of 300 and 3000 pmol kg(-1), all three peptides caused dose-dependent tachycardia and hypotension, with rapid-onset, short-duration, mesenteric vasodilatation and slower-onset, more prolonged hindquarters vasodilatation but little or no change in renal vascular conductance. Pretreatment with the nonselective CRF receptor antagonist astressin or the selective CRF(2) receptor antagonist antisauvagine 30 abolished all the cardiovascular actions of all three peptides. Indomethacin had no effect on responses to hUCN2, and there was no evidence for any involvement of nitric oxide (NO) in the vasodilator actions of hUCN2. There was no evidence that recruitment of angiotensin- and endothelin-mediated vasoconstrictor mechanisms counteracted the vascular actions of hUCN2. The results indicate that the hemodynamic effects of i.v. hUCN2, mUCN2, and CRF depend on activation of CRF(2) receptors and do not involve NO or prostanoids.
在清醒的雄性Sprague-Dawley大鼠中，我们比较了选择性促肾上腺皮质激素释放因子2型（CRF(2)）受体配体人尿皮质素2和小鼠尿皮质素2（分别为hUCN2和mUCN2）与CRF的局部血流动力学作用。静脉推注剂量为3和30 pmol kg(-1)的hUCN2、mUCN2或CRF没有显著的血流动力学作用，但在剂量为300和3000 pmol kg(-1)时，所有三种肽均引起剂量依赖性心动过速和低血压，伴有快速起效、持续时间短的肠系膜血管舒张以及起效较慢、持续时间更长的后肢血管舒张，但肾血管传导几乎没有变化或没有变化。用非选择性CRF受体拮抗剂阿斯特辛或选择性CRF(2)受体拮抗剂抗 sauvagine 30预处理可消除所有三种肽的所有心血管作用。吲哚美辛对hUCN2的反应没有影响，并且没有证据表明一氧化氮（NO）参与hUCN2的血管舒张作用。没有证据表明血管紧张素和内皮素介导的血管收缩机制的募集抵消了hUCN2的血管作用。结果表明，静脉注射hUCN2、mUCN2和CRF的血流动力学效应取决于CRF(2)受体的激活，并且不涉及NO或前列腺素。
