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

Abstract

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.