Renal sodium/calcium exchange; a vasodilator that is defective in salt-sensitive hypertension.
The Na+ : Ca2+ exchanger is an important plasma membrane ion transport pathway that plays a major role in controlling [Ca2+]i. In smooth muscle cells, it may function as a Ca2+ extrusion pathway and may help lower [Ca2+]i in response to vasoconstrictor-induced increases in [Ca2+]i. It may also extrude [Ca2+]i and lead to vasodilation in response to vasodilators. Our recent studies have been performed to determine the existence and regulation of the Na+ : Ca2+ exchanger in renal contractile cells which include afferent and efferent arterioles and mesangial cells. Exchanger activity is present in all three of these contractile elements but is higher in afferent arterioles vs. efferent arterioles. We have also examined the role of altered regulation of the exchanger in the SHR and in salt-sensitive hypertension. With the establishment of high blood pressure, Na+ : Ca2+ exchanger activity is reduced in afferent but not in efferent arterioles in both models of hypertension. Other works in cultured mesangial cells and freshly dissected afferent arterioles, have shown that protein kinase C (PKC) up-regulates the Na+ : Ca2+ exchanger from Dahl/Rapp salt-resistant rats while it fails to do so in arterioles and mesangial cells from salt-sensitive rats. This defect in PKC regulation of Na+ : Ca2+ exchange is the result of a loss of PKC-mediated translocation of the exchanger to the plasma membrane in S mesangial cells. Thus, a defect in the PKC-Na+ : Ca2+ exchanger-translocation pathway may cause dysregulation of [Ca2+]i and help explain the dramatic decrease in GFR that occurs in this model of hypertension.
Bell
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PD
Nephrology Research and Training Center, Departments of Medicine and Physiology, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Mashburn
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N
Unlap
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MT
D000818:Animals; D001160:Arterioles / Q000378:metabolism; D003001:Cloning, Molecular; D004351:Drug Resistance; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology*; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000502:physiology*; D014664:Vasodilation
D019831:Sodium-Calcium Exchanger; D012965:Sodium Chloride; D011493:Protein Kinase C