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 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.
Solomon
S G
SG
Department of Physiology, University of Sydney, NSW, Australia.
Llewellyn-Smith
I J
IJ
Minson
J B
JB
Arnolda
L F
LF
Chalmers
J P
JP
Pilowsky
P M
PM
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D007278:Injections, Spinal; D054833:Isoindoles; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000737:chemistry / Q000166:cytology / Q000502:physiology