This Article Full Text Full Text (PDF) All Versions of this Article: 42/3/363    most recent 01.HYP.0000084060.54314.F5v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Unlap, M. T. Articles by Bell, P. D. Search for Related Content PubMed PubMed Citation Articles by Unlap, M. T. Articles by Bell, P. D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL HYDROGEN PEROXIDE Related Collections Animal models of human disease Hypertension - basic studies Genetics of cardiovascular disease

(Hypertension. 2003;42:363.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Na⁺/Ca²⁺ Exchanger

Target for Oxidative Stress in Salt-Sensitive Hypertension

M. Tino Unlap; Elizabeth Bates; Corey Williams; Peter Komlosi; Iantha Williams; Gergely Kovacs; Brian Siroky; P. Darwin Bell

From the Nephrology Research and Training Center, Departments of Medicine and Physiology, Division of Nephrology, University of Alabama at Birmingham.

Correspondence to M. Tino Unlap, PhD, University of Alabama at Birmingham, UAB Station, 865 Sparks Ctr, Birmingham, AL 35294. E-mail unlap{at}uab.edu

The Na⁺/Ca²⁺ exchanger regulates intracellular calcium ([Ca²⁺]_i), and attenuation of Na⁺/Ca²⁺ exchange by oxidative stress might lead to dysregulation of [Ca²⁺]_i. We have shown that the Na⁺/Ca²⁺ 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⁺/Ca²⁺ 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 ⁴⁵Ca²⁺ uptake (reverse mode) and [Ca²⁺]_i elevation (forward mode) in the presence and absence of H₂O₂ and peroxynitrite. Our results showed that ⁴⁵Ca²⁺ uptake in SNCX cells was attenuated at 500 and 750 µmol/L H₂O₂ (63±12% and 25±7%, respectively; n=16) and at 50 and 100 µmol/L peroxynitrite (47±9% and 22±9%, respectively; n=16). In RNCX cells, ⁴⁵Ca²⁺ uptake was attenuated at only 750 and 100 µmol/L H₂O₂ and peroxynitrite (61±9% and 63±6%, respectively; n=16). In addition, the elevation in [Ca²⁺]_i was greater in SNCX cells than in RNCX cells in response to 750 µmol/L H₂O₂ (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 [Ca²⁺]_i that is found in this model of salt-sensitive hypertension.

Key Words: ion transport • oxidative stress • hypertension, sodium-dependent • calcium

This article has been cited by other articles:

				M.-J. Lin, X.-R. Yang, Y.-N. Cao, and J. S. K. Sham Hydrogen peroxide-induced Ca2+ mobilization in pulmonary arterial smooth muscle cells Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1598 - L1608. [Abstract] [Full Text] [PDF]