Affiliation:
1. From the Nephrology Research and Training Center, Departments of Medicine and Physiology, Division of Nephrology, University of Alabama at Birmingham.
Abstract
The Na
+
/Ca
2+
exchanger regulates intracellular calcium ([Ca
2+
]
i
), and attenuation of Na
+
/Ca
2+
exchange by oxidative stress might lead to dysregulation of [Ca
2+
]
i
. We have shown that the Na
+
/Ca
2+
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
2+
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
45
Ca
2+
uptake (reverse mode) and [Ca
2+
]
i
elevation (forward mode) in the presence and absence of H
2
O
2
and peroxynitrite. Our results showed that
45
Ca
2+
uptake in SNCX cells was attenuated at 500 and 750 μmol/L H
2
O
2
(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,
45
Ca
2+
uptake was attenuated at only 750 and 100 μmol/L H
2
O
2
and peroxynitrite (61±9% and 63±6%, respectively; n=16). In addition, the elevation in [Ca
2+
]
i
was greater in SNCX cells than in RNCX cells in response to 750 μmol/L H
2
O
2
(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
2+
]
i
that is found in this model of salt-sensitive hypertension.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
14 articles.
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