Blockade of non-NMDA receptors attenuates reflex pressor response to static contraction.
Considerable evidence suggests that both substance P and glutamate play a role in the spinal transmission of the exercise pressor reflex. We tested two hypotheses. First, after a lumbosacral intrathecal injection of a glutamatergic receptor antagonist, the reflex cardiovascular and ventilatory responses to static contraction are attenuated. Second, after a lumbosacral intrathecal injection of a substance P receptor antagonist and a glutamatergic receptor antagonist, the reflex cardiovascular and ventilatory responses to static contraction are abolished. We found that 1) the reflex cardiovascular responses to static contraction were unaffected (P > 0.05) after the intrathecal injection of the N-methyl-D-aspartate (NMDA) receptor antagonists, dl-2-amino-5-phosphonopentanoate (+/- AP-5) or 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (+/- CPP); 2) the reflex pressor response to static muscular contraction was attenuated by > 50% after the intrathecal injection of the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); and 3) the reflex pressor response to static contraction was almost abolished after the intrathecal injection of the substance P receptor antagonist, CP-96,345, and CNQX. Our results suggest that substance P and glutamate are two neurotransmitters involved in the spinal transmission of the exercise pressor reflex and that substance P and glutamate exert their effects via neurokinin-1 (NK-1) and non-NMDA receptors, respectively.
Hill
J M
JM
Department of Internal Medicine, University of California, Davis 95616.
Pickar
J G
JG
Kaufman
M P
MP
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000494:pharmacology*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002415:Cats; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D064729:Neurokinin-1 Receptor Antagonists; D010879:Piperazines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C066892:CP 96345