Attenuation of reflex pressor and ventilatory responses to static contraction by an NK-1 receptor antagonist.
The chemical messengers released onto second-order dorsal horn neurons from the spinal terminals of contraction-activated group III and IV muscle afferents have not been identified. One candidate is the tachykinin substance P. Related to substance P are two other tachykinins, neurokinin A (NKA) and neurokinin B (NKB), which, like substance P, have been isolated in the dorsal horn of the spinal cord and have receptors there. Whether NKA or NKB plays a transmitter/modulator role in the spinal processing of the exercise pressor reflex is unknown. Therefore, we tested the following hypotheses. After the intrathecal injection of a highly selective NK-1 (substance P) receptor antagonist onto the lumbosacral spinal cord, the reflex pressor and ventilatory responses to static muscular contraction will be attenuated. Likewise, after the intrathecal injection either of an NK-2 (NKA) receptor antagonist or an NK-3 (NKB) receptor antagonist onto the lumbrosacral spinal cord, the reflex pressor and ventilatory responses to static contraction will be attenuated. We found that, 10 min after the intrathecal injection of 100 micrograms of the NK-1 receptor antagonist, the pressor and ventilatory responses to contraction were significantly (P < 0.05) attenuated. Mean arterial pressure was attenuated by 13 +/- 3 mmHg (48%) and minute volume of ventilation by 120 +/- 38 ml/min (34%). The cardiovascular and ventilatory responses to contraction before either 100 micrograms of the NK-2 receptor antagonist or 100 micrograms of the NK-3 receptor antagonist were not different (P > 0.05) from those after the NK-2 or the NK-3 receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Hill
J M
JM
Department of Internal Medicine, University of California, Davis 95616.
Pickar
J G
JG
Kaufman
M P
MP
D000595:Amino Acid Sequence; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D006339:Heart Rate / Q000187:drug effects; D007278:Injections, Spinal; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000187:drug effects; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D015287:Neurokinin B / Q000037:antagonists & inhibitors; D005082:Physical Exertion / Q000187:drug effects / Q000502:physiology*; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D015656:Respiratory Mechanics / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects
D001713:Biphenyl Compounds; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D015288:Neurokinin A; D015287:Neurokinin B; C066892:CP 96345