Kerecsen L, Bunag R D
Department of Pharmacology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City.
J Pharmacol Exp Ther. 1989 Nov;251(2):645-9.
To compare the cardiovascular effects of chronic monoamine oxidase (MAO) A and B inhibition, rats were given s.c. injections of saline clorgyline or l-deprenyl daily for 3 weeks. Indwelling vascular catheters and a Doppler flow probe were implanted chronically to allow subsequent recording of femoral pressure, heart rate and iliac blood flow before and during the treatment while the rats were awake. On days 7 and 21, average femoral pressure were significantly higher in rats treated with either saline or l-deprenyl than in those treated with clorgyline. Pressor responses elicited by injecting graded doses of phenylephrine, angiotensin or tyramine i.v. were always accompanied by bradycardia and reduced iliac flow. Magnitude of all responses was unaltered in control rats treated with the saline vehicle. In rats treated with l-deprenyl responses to tyramine were enhanced slightly, but in those treated with clorgyline enhancement was more pronounced and included not only responses to tyramine but also those to phenylephrine and angiotensin. Because clorgyline inhibits MAO A whereas l-deprenyl inhibits MAO B our findings imply that enhanced pressor responsiveness depends on inhibition of MAO A rather than MAO B.
为比较慢性单胺氧化酶(MAO)A和B抑制作用对心血管系统的影响,给大鼠皮下每日注射生理盐水、氯吉兰或L-司来吉兰,持续3周。长期植入血管导管和多普勒血流探头,以便在大鼠清醒状态下,于治疗前及治疗期间记录股动脉血压、心率和髂血流量。在第7天和第21天,接受生理盐水或L-司来吉兰治疗的大鼠平均股动脉血压显著高于接受氯吉兰治疗的大鼠。静脉注射不同剂量的去氧肾上腺素、血管紧张素或酪胺所引发的升压反应总是伴有心动过缓和髂血流量减少。用生理盐水载体处理的对照大鼠中,所有反应的幅度均未改变。在接受L-司来吉兰治疗的大鼠中,对酪胺的反应略有增强,但在接受氯吉兰治疗的大鼠中,增强更为明显,不仅包括对酪胺的反应,还包括对去氧肾上腺素和血管紧张素的反应。由于氯吉兰抑制MAO A,而L-司来吉兰抑制MAO B,我们的研究结果表明,升压反应性增强取决于对MAO A的抑制,而非MAO B。