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 (Ca2+) 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 Ca2+ concentration in the cytosol ([Ca2+]c), endoplasmic reticulum ([Ca2+]er), and mitochondria ([Ca2+]m). We found the following differences on calcium handling in SHRs, as compared with NWR: (i) higher basal [Ca2+]c and basal [Ca2+]m; (ii) greater [Ca2+]c elevations elicited by acetylcholine and K+, with faster activation but slower inactivation; (iii) greater [Ca2+]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 [Ca2+]c and [Ca2+]m suggest an enhanced mitochondrial Ca2+ uptake, and the greater [Ca2+]c elevations produced by FCCP indicates a higher mitochondrial Ca2+ release into the cytosol. This alteration of intracellular Ca2+ movements could explain the greater quantal catecholamine release responses seen in SHRs, as compared with NWRs in previous studies. Furthermore, enhanced mitochondrial Ca2+ cycling may be the basis for the dysfunction of mitochondrial bioenergetics, reported to be present in hypertensive states.