Chemoreceptor hypersensitivity, sympathetic excitation, and overexpression of ASIC and TASK channels before the onset of hypertension in SHR

Z-Y Tan, Y Lu, C A Whiteis, A E Simms, JFR Paton, M W Chapleau, F M Abbdoud

Research output: Contribution to journalArticle (Academic Journal)peer-review

83 Citations (Scopus)

Abstract

RATIONALE: 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. METHODS AND 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.
Translated title of the contributionChemoreceptor hypersensitivity, sympathetic excitation, and overexpression of ASIC and TASK channels before the onset of hypertension in SHR
Original languageEnglish
Pages (from-to)536 - 545
Number of pages10
JournalCirculation Research
Volume106
Issue number3
Early online date17 Dec 2009
DOIs
Publication statusPublished - 19 Feb 2010

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