Gardiner S M, March J E, Kemp P A, Bennett T
Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, United Kingdom.
J Pharmacol Exp Ther. 2007 Apr;321(1):221-6. doi: 10.1124/jpet.106.116962. Epub 2007 Jan 19.
The aims of the study were, in conscious Sprague-Dawley rats, to compare the effects of stresscopin-related peptide (SRP) and urocortin (UCN) 1 on blood pressure, heart rate, and regional hemodynamics; to determine whether or not there were residual tachycardic effects of SRP or UCN1 after cardiac autonomic blockade; and to investigate a possible involvement of corticotropin releasing factor type 1 (CRF1) receptor-mediated histamine release in the vasodilator actions of UCN1. SRP and UCN1 (both at 3 nmol/kg i.v.) caused hypotension, tachycardia, and mesenteric and hindquarters vasodilatation, but the magnitude and/or duration of the effects of UCN1 were generally greater than those of SRP. Pretreatment with atropine plus propranolol abolished the tachycardic effects of SRP and UCN1, and, under those conditions, the hypotensive effect of SRP, but not that of UCN1, was enhanced, probably because the hindquarters vasodilator effect of the latter was also reduced. Pretreatment with mepyramine plus cimetidine had no effect on the hemodynamic actions of either SRP or UCN1. It is concluded that, in conscious rats, the tachycardic effects of SRP and UCN1 are due to autonomic nervous activation mainly through baroreflex mechanisms. There is no evidence for an involvement of CRF1 receptor-mediated histamine release in the vasodilator actions of UCN1, but a propranolol-sensitive hindquarters vasodilator action of UCN, but not of SRP, was identified.
本研究的目的是,在清醒的斯普拉格-道利大鼠中,比较应激原相关肽(SRP)和尿皮质素(UCN)1对血压、心率和局部血流动力学的影响;确定心脏自主神经阻滞后SRP或UCN1是否存在残余的心动过速效应;并研究促肾上腺皮质激素释放因子1型(CRF1)受体介导的组胺释放是否可能参与UCN1的血管舒张作用。SRP和UCN1(均为静脉注射3 nmol/kg)均引起低血压、心动过速以及肠系膜和后肢血管舒张,但UCN1作用的幅度和/或持续时间通常大于SRP。用阿托品加普萘洛尔预处理可消除SRP和UCN1的心动过速效应,在这些条件下,SRP的降压效应增强,而UCN1的降压效应未增强,这可能是因为后者的后肢血管舒张效应也降低了。用美吡拉敏加西咪替丁预处理对SRP或UCN1的血流动力学作用均无影响。得出的结论是,在清醒大鼠中,SRP和UCN1的心动过速效应主要是由于自主神经激活,主要通过压力反射机制。没有证据表明CRF1受体介导的组胺释放参与UCN1的血管舒张作用,但发现UCN存在普萘洛尔敏感的后肢血管舒张作用,而SRP不存在。