Greater cytosolic and mitochondrial calcium transients in adrenal medullary slices of hypertensive, compared with normotensive rats

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.Governments of Spain and BrazilDepartamento de Farmacologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, BrazilInstituto Teal Hernando Facultad de Medicina, Universidad Autonoma de Madrid, SpainUniversidad Autonoma de Madrid, Spain (AGG) and Universidade Federal de São Paulo, Escola Paulista de Medicina, BrazilRETICS, Instituto de Salud Carlos IIIComunidad de MadridMICINN, SpainAgencia Lain Entralgo, Comunidad de MadridFundacion C.I.E.N., Instituto de Salud Carlos IIIUniv Autonoma Madrid, Fac Med, Inst Teofilo Hernando, E-28029 Madrid, SpainUniversidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, São Paulo, BrazilUniv Autonoma Madrid, Fac Med, Dept Farmacol & Terapeut, E-28029 Madrid, SpainUniv Autonoma Madrid, Hosp Univ Princesa, Serv Farmacol Clin, Madrid 28006, SpainUniversidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, São Paulo, BrazilGovernments of Spain and Brazil: PHB 2005-0018-PCComunidad de Madrid: S-SAL-0275-2006MICINN, Spain: SAF2006-03589MICINN, Spain: SAF2007-65181Agencia Lain Entralgo, Comunidad de Madrid: NDE 07/9Fundacion C.I.E.N., Instituto de Salud Carlos III: PI016/09: RD 06/0026Web of Scienc