Vanilloid type 1 receptor and the acid-sensing ion channel mediate acid phosphate activation of muscle afferent nerves in rats

Zhaohui Gao, Oze Henig, Valerie Kehoe, Lawrence I. Sinoway, Jianhua Li

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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, vanilloid type 1 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 by 25 ± 2 mmHg, whereas monoprotonated phosphate (HPO42, pH 7.5) had no effect. Pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (a purinergic 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, VR1 and ASIC mediate the pressor response due to H2PO4-. The H2PO4--evoked response was greater when VR1 and ASIC blockers were given simultaneously than when the respective blockers were given separately. Our laboratory's 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 H2PO4-. Furthermore, the physiological mechanisms mediating the response to H+ and H2PO4- are likely to be different.

Original languageEnglish (US)
Pages (from-to)421-426
Number of pages6
JournalJournal of applied physiology
Volume100
Issue number2
DOIs
StatePublished - Feb 2006

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

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