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J Appl Physiol (October 6, 2005). doi:10.1152/japplphysiol.00659.2005
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Submitted on June 6, 2005
Accepted on September 29, 2005

Vanilloid Type 1 Receptor and the Acid Sensing Ion Channel Mediate Acid Phosphate Activation of Muscle Afferent Nerves in Rats

Zhaohui Gao1, Oze Henig1, Valerie Kehoe1, Lawrence I. Sinoway2, and Jianhua Li1*

1 Department of Medicine/Cardiology, Pennsylvania State University College of Medicine, Hershey, PA, USA
2 Department of Medicine/Cardiology, Pennsylvania State University College of Medicine, Hershey, PA, USA; Department of Medicine, Lebanon VA Medical Center, Lebanon, PA, USA

* To whom correspondence should be addressed. E-mail: jianhuali{at}psu.edu.

Reflex cardiovascular responses to contracting skeletal muscle are mediated by mechanical and metabolic stimulation of thin fiber muscle afferents. Diprotonated phosphate (H2PO4-) excites those thin fiber nerves and evokes the muscle pressor reflex. The receptors mediating this response are unknown. Thus, we examined the role played by purinergic receptors (P2X), vanilloid type I receptors (VR1) and acid-sensing ion channels (ASIC) in mediating H2PO4- evoked pressor responses. Phosphate and blocking agents were injected into the arterial blood supply of the hindlimb muscles of 53 decerebrated rats. H2PO4- (86 mM, pH 6.0) increased mean arterial pressure (MAP) by 25 ± 2 mmHg whereas monoprotonated phosphate (HPO42-, pH 7.5) had no effect. Pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; a P2X receptor antagonist, 2 mM) did not block the response. However, capsazepine (a VR1 antagonist, 1 mg/kg) attenuated the reflex by 60% and amiloride (an ASIC blocker, 6 µg/kg) by 52%. Of note, the H2PO4- induced pressor response was attenuated by 87% when both capsazepine and amiloride were injected before the H2PO4-. In conclusion, VRI and ASIC mediate the pressor response due to H2PO4-. The H2PO4- evoked response was greater when VRI and ASIC blockers were given simultaneous then when the respective blockers were given separately. Our previous study has shown that H+ stimulates ASIC (but not VR1) on thin fiber afferent nerves in evoking the reflex response. Thus VR1 and ASIC are likely to play a coordinated and interactive role in processing the muscle afferent response to diprotonated phosphate. Furthermore, the physiologic mechanisms mediating the response to H+ and H2PO4- are likely to be different.




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