Neurokinin-1 receptors and spinal cord control of blood pressure in spontaneously hypertensive rats

In this study we examined blood pressure and heart rate responses to intrat hecal administration of a synthetic NK1-receptor agonist, H2N-(CH2)(4)-CO-P he-Phe-Pro-NmeLeu-Met-NH2 (GR 73,632), in spontaneously hypertensive rats ( SHR) and their progenitor strain, the Wistar-Kyoto rat (WKY). Sodium pentob arbitone anaesthetised rats with implanted intrathecal catheters were paral ysed (pancuronium dibromide) and artificially ventilated. Injection of GR 7 3,632 at the T9 spinal level evoked dose-dependent increases in mean arteri al pressure (MAP) in WKY and SHR. SHR had a lower MAP response threshold th an WKY but increase in response with increasing dose was less in SHR than W KY. Biphasic blood pressure responses at high doses were observed in both s trains. Prior administration of the NK1-receptor antagonist (3 aR,7aR)-7,7- diphenyl-2-[1-imino-2(methoxyphenyl)ethyl] perhydroisoindol-4-one (RP 67,58 0) significantly reduced the pressor response in WKY but not SHR. The depre ssor response was not attenuated in either strain. (C) 1999 Elsevier Scienc e B.V. All rights reserved.