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.
Miranda-Ferreira
Regiane
R
Departamento de Farmacología, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
de Pascual
Ricardo
R
Smaili
Soraya S
SS
Caricati-Neto
Afonso
A
Gandía
Luis
L
García
Antonio G
AG
Jurkiewicz
Aron
A
D000109:Acetylcholine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009068:Movement / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D012433:Ryanodine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002110:Caffeine; D019284:Thapsigargin; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D016257:Fura-2