Spinal P2X receptor modulates muscle pressor reflex via glutamate.
Static contraction of skeletal muscle evokes reflex increases in blood pressure and heart rate. Previous studies showed that P2X receptors located at the dorsal horn of the spinal cord play a role in modulating the muscle pressor reflex. P2X stimulation can alter release of the excitatory amino acid, glutamate (Glu). In this report, we tested the hypothesis that stimulation of P2X receptors enhances the concentrations of Glu ([Glu]) in the dorsal horn, and that blocking P2X receptors attenuates contraction-induced Glu increases and the resultant reflex pressor response. Contraction was elicited by electrical stimulation of the L(7) and S(1) ventral roots of 14 cats. Glu samples were collected from microdialysis probes inserted in the L(7) level of the dorsal horn of the spinal cord, and dialysate [Glu] was determined using the HPLC method. First, microdialyzing alpha,beta-methylene ATP (0.4 mM) into the dorsal horn significantly increased [Glu]. In addition, contraction elevated [Glu] from baseline of 536 +/- 53 to 1,179 +/- 192 nM (P < 0.05 vs. baseline), and mean arterial pressure by 39 +/- 8 mmHg in the control experiment. Microdialyzing the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (10 mM) into the dorsal horn attenuated the contraction induced-Glu increase (610 +/- 128 to 759 +/- 147 nM; P > 0.05) and pressor response (16 +/- 3 mmHg, P < 0.05 vs. control). Our findings demonstrate that P2X modulates the cardiovascular responses to static muscle contraction by affecting the release of Glu in the dorsal horn of the spinal cord.
Li
Jianhua
J
Department of Medicine, Heart and Vascular Institute, Penn State College of Medicine, Milton S Hershey MedicalCenter, Hershey, Pennsylvania 17033, USA.
Lu
Jian
J
Gao
Zhaohui
Z
Koba
Satoshi
S
Xing
Jihong
J
King
Nicholas
N
Sinoway
Lawrence
L
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D012018:Reflex / Q000502:physiology
D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D018698:Glutamic Acid; D011732:Pyridoxal Phosphate