Chemoreceptor hypersensitivity, sympathetic excitation, and overexpression of ASIC and TASK channels before the onset of hypertension in SHR.
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.
Tan
Zhi-Yong
ZY
Cardiovascular Center, University of Iowa, Iowa City, USA.
Lu
Yongjun
Y
Whiteis
Carol A
CA
Simms
Annabel E
AE
Paton
Julian F R
JF
Chapleau
Mark W
MW
Abboud
François M
FM
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
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