title: Role of diprotonated phosphate in evoking muscle reflex responses in cats and humans.
abstract: Lactic acid and H+ evoke muscle reflexes that raise sympathetic nerve activity. Whether these substances are direct afferent stimulants or markers for the acidification of other substances is unknown. Diprotonated phosphate (H2PO4-), a possible mediator of fatigue, increases as the cell acidifies and phosphate is produced. Its role in evoking muscle reflexes is unknown. We used 31P-nuclear magnetic resonance to measure forearm muscle H+ and H2PO4- and microneurography to measure muscle sympathetic nerve activity (MSNA, peroneal nerve) during a handgrip protocol designed to dissociate H+ from H2PO4-. Ischemic handgrip (50% maximal voluntary contraction x 2 min) was followed by a 1-min rest period during which the muscle was freely perfused. This was followed by a second bout of ischemic handgrip and a 5-min recovery. In seven of eight subjects, MSNA correlated with H2PO4-, whereas it correlated with pH in only one subject. To determine whether muscle reflex responses are evoked by H+, lactic acid, monoprotonated phosphate (HPO4(2-), or H2PO4-, we injected H+, lactate, H2PO4- [all 50 mM in 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffered to pH 6], and HPO4(2-) (50 mM, pH 7.5 in 10 mM HEPES) into the arterial supply of the triceps surae of the cat (n = 9) as we measured mean arterial blood pressure (MAP). H2PO4- increased MAP more than HPO4(2-), H+, or lactate (27.1 +/- 3.7 vs. 5.0 +/- 1.3, 4.6 +/- 3.1, and 7.7 +/- 3.2 rise in mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
authors.forename: L I
authors.initials: LI
authors.lastname: Sinoway
authors.forename: M B
authors.initials: MB
authors.lastname: Smith
authors.forename: B
authors.initials: B
authors.lastname: Enders
authors.forename: U
authors.initials: U
authors.lastname: Leuenberger
authors.forename: T
authors.initials: T
authors.lastname: Dzwonczyk
authors.forename: K
authors.initials: K
authors.lastname: Gray
authors.forename: S
authors.initials: S
authors.lastname: Whisler
authors.forename: R L
authors.initials: RL
authors.lastname: Moore
mesh_terms: D000328:Adult; D000818:Animals; D002415:Cats; D005542:Forearm; D006531:HEPES / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D009682:Magnetic Resonance Spectroscopy; D009119:Muscle Contraction; D009132:Muscles / Q000294:innervation / Q000502:physiology*; D009994:Osmolar Concentration; D010543:Peroneal Nerve / Q000502:physiology; D010710:Phosphates / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D012996:Solutions; D013564:Sympathetic Nervous System / Q000502:physiology
chemical_list: D007773:Lactates; D010710:Phosphates; D012996:Solutions; D019344:Lactic Acid; D006531:HEPES