title: Chemoreceptor hypersensitivity, sympathetic excitation, and overexpression of ASIC and TASK channels before the onset of hypertension in SHR.
abstract: BACKGROUND
  Increased sympathetic nerve activity has been linked to the pathogenesis of hypertension in humans and animal models. Enhanced peripheral chemoreceptor sensitivity which increases sympathetic nerve activity has been observed in established hypertension but has not been identified as a possible mechanism for initiating an increase in sympathetic nerve activity before the onset of hypertension.
  
  
  OBJECTIVE
  We tested this hypothesis by measuring the pH sensitivity of isolated carotid body glomus cells from young spontaneously hypertensive rats (SHR) before the onset of hypertension and their control normotensive Wistar-Kyoto (WKY) rats.
  
  
  RESULTS
  We found a significant increase in the depolarizing effect of low pH in SHR versus WKY glomus cells which was caused by overexpression of 2 acid-sensing non-voltage-gated channels. One is the amiloride-sensitive acid-sensing sodium channel (ASIC3), which is activated by low pH and the other is the 2-pore domain acid-sensing K(+) channel (TASK1), which is inhibited by low pH and blocked by quinidine. Moreover, we found that the increase in sympathetic nerve activity in response to stimulation of chemoreceptors with sodium cyanide was markedly enhanced in the still normotensive young SHR compared to control WKY rats.
  
  
  CONCLUSIONS
  Our results establish a novel molecular basis for increased chemotransduction that contributes to excessive sympathetic activity before the onset of hypertension.
authors.affiliation: Cardiovascular Center, University of Iowa, Iowa City, USA.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Tan
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Lu
authors.forename: Carol A
authors.initials: CA
authors.lastname: Whiteis
authors.forename: Annabel E
authors.initials: AE
authors.lastname: Simms
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
authors.forename: Mark W
authors.initials: MW
authors.lastname: Chapleau
authors.forename: François M
authors.initials: FM
authors.lastname: Abboud
mesh_terms: D062565:Acid Sensing Ion Channels; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002344:Carotid Body / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010791:Phrenic Nerve / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015222:Sodium Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012966:Sodium Cyanide / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013997:Time Factors
chemical_list: C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D015222:Sodium Channels; C420132:potassium channel subfamily K member 3; D000584:Amiloride; D011802:Quinidine; D012966:Sodium Cyanide