Na+/Ca2+ exchanger: Target for oxidative stress in salt-sensitive hypertension

Academic Article

Abstract

  • The Na /Ca exchanger regulates intracellular calcium ([Ca ] . and attenuation of Na /Ca exchange by oxidative stress might lead to dysregulation of [Ca ] . We have shown that the Na /Ca exchanger differs functionally and at the amino acid level between salt-sensitive and salt-resistant rats. Therefore, the purpose of these studies was to determine how oxidative stress affects the activities of the 2 Na /Ca exchangers that we cloned from mesangial cells of salt-resistant (RNCX) and salt-sensitive (SNCX) Dahl/Rapp rats. The effects of oxidative stress on exchanger activity were examined in cells expressing RNCX or SNCX by assessing Ca uptake (reverse mode) and [Ca ] elevation (forward mode) in the presence and absence of H O and peroxynitrite. Our results showed that Ca uptake in SNCX cells was attenuated at 500 and 750 μmol/L H O (63±12% and 25±7%, respectively; n = 16) and at 50 and 100 μmol/L peroxynitrite (47±9% and 22±29%, respectively; n = 16). In RNCX cells, Ca uptake was attenuated at only 750 and 100 μmol/L H O and peroxynitrite (61±9% and 63±6%, respectively; n = 16). In addition, the elevation in [Ca ] was greater in SNCX cells than in RNCX cells in response to 750 μmol/L H O (58±5.5 vs 17±4.1 nmol/L; n = 13) and 100 μmol/L peroxynitrite (33±5 vs 11±6 nmol/L; n = 19). The enhanced impairment of SNCX activity by oxidative stress might contribute to the dysregulation of [Ca ] that is found in this model of salt-sensitive hypertension. + 2+ 2+ + 2+ 2+ + 2+ + 2+ 45 2+ 2+ 45 2+ 45 2+ 2+ 2+ i i i 2 2 2 2 2 2 i 2 2 i
  • Published In

  • Hypertension  Journal
  • Digital Object Identifier (doi)

    Author List

  • Unlap MT; Bates E; Williams C; Komlosi P; Williams I; Kovacs G; Siroky B; Bell PD
  • Start Page

  • 363
  • End Page

  • 368
  • Volume

  • 42
  • Issue

  • 3