Solomon S G, Llewellyn-Smith I J, Minson J B, Arnolda L F, Chalmers J P, Pilowsky P M
Department of Physiology, University of Sydney, NSW, Australia.
Brain Res. 1999 Jan 2;815(1):116-20. doi: 10.1016/s0006-8993(98)01107-x.
In this study we examined blood pressure and heart rate responses to intrathecal administration of a synthetic NK1-receptor agonist, H2N-(CH2)4-CO-Phe-Phe-Pro-NmeLeu-Met-NH2 (GR 73,632), in spontaneously hypertensive rats (SHR) and their progenitor strain, the Wistar-Kyoto rat (WKY). Sodium pentobarbitone anaesthetised rats with implanted intrathecal catheters were paralysed (pancuronium dibromide) and artificially ventilated. Injection of GR 73,632 at the T9 spinal level evoked dose-dependent increases in mean arterial pressure (MAP) in WKY and SHR. SHR had a lower MAP response threshold than WKY but increase in response with increasing dose was less in SHR than WKY. Biphasic blood pressure responses at high doses were observed in both strains. Prior administration of the NK1-receptor antagonist (3 aR,7aR)-7,7-diphenyl-2-[1-imino-2(methoxyphenyl)ethyl] perhydroisoindol-4-one (RP 67,580) significantly reduced the pressor response in WKY but not SHR. The depressor response was not attenuated in either strain.
在本研究中,我们检测了鞘内注射合成的NK1受体激动剂H2N-(CH2)4-CO-Phe-Phe-Pro-NmeLeu-Met-NH2(GR 73,632)对自发性高血压大鼠(SHR)及其亲代品系Wistar-Kyoto大鼠(WKY)血压和心率的影响。用戊巴比妥钠麻醉并植入鞘内导管的大鼠使用泮库溴铵使其麻痹并进行人工通气。在T9脊髓水平注射GR 73,632可引起WKY和SHR平均动脉压(MAP)的剂量依赖性升高。SHR的MAP反应阈值低于WKY,但随着剂量增加,SHR的反应增加幅度小于WKY。在两个品系中均观察到高剂量时的双相血压反应。预先给予NK1受体拮抗剂(3 aR,7aR)-7,7-二苯基-2-[1-亚氨基-2-(甲氧基苯基)乙基]全氢异吲哚-4-酮(RP 67,580)可显著降低WKY的升压反应,但对SHR无效。两个品系的降压反应均未减弱。