Greater cytosolic and mitochondrial calcium transients in adrenal medullary slices of hypertensive, compared with normotensive rats
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2010-06-25
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Miranda-Ferreira, Regiane [UNIFESP]
Pascual, Ricardo de
Smaili, Soraya Soubhi [UNIFESP]
Caricati-Neto, Afonso [UNIFESP]
Gandia, Luis
Garcia, Antonio G.
Jurkiewicz, Aron [UNIFESP]
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Pronounced differences in the kinetics of single-vesicle catecholamine release from adrenal chromaffin cells stimulated with acetylcholine or high potassium (K(+)) have been recently found between normotensive Wistar rats (NWRs) and spontaneously hypertensive rats (SHRs). Such differences could be explained on the basis of distinct mechanisms of calcium (Ca(2+)) handling by chromaffin cells of NWRs and SHRs. We have explored here this hypothesis in adrenal medullary slices loaded with calcium fluorescent probes to measure the changes in Ca(2+) concentration in the cytosol ([Ca(2+)](c)), endoplasmic reticulum ([Ca(2+)](er)), and mitochondria ([Ca(2+)](m)). We found the following differences on calcium handling in SHRs, as compared with NWR: (i) higher basal [Ca(2+)](c) and basal [Ca(2+)](m); (ii) greater [Ca(2+)](c) elevations elicited by acetylcholine and K(+), with faster activation but slower inactivation; (iii) greater [Ca(2+)](c) elevations elicited by CRT (a mixture of caffeine, ryanodine, and thapsigargin) and by the mitochondrial protonophore FCCP (carbonylcyanide p-(trifluoromethoxy) phenylhydrazone). the higher basal [Ca(2+)](c) and [Ca(2+)](m) suggest an enhanced mitochondrial Ca(2+) uptake, and the greater [Ca(2+)](c) elevations produced by FCCP indicates a higher mitochondrial Ca(2+) release into the cytosol. This alteration of intracellular Ca(2+) movements could explain the greater quantal catecholamine release responses seen in SHRs, as compared with NWRs in previous studies. Furthermore, enhanced mitochondrial Ca(2+) cycling may be the basis for the dysfunction of mitochondrial bioenergetics, reported to be present in hypertensive states. (C) 2010 Elsevier B.V. All rights reserved.
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European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 636, n. 1-3, p. 126-136, 2010.