Chronic intermittent hypoxia increases chromaffin cell secretory capacity through a reactive oxygen species mediated, protein kinase C dependent pathway

Abstract

Chronic intermittent hypoxia (CIH) augments sympathetic‐evoked catecholamine release from the adrenal medulla. In the present study we examine the effects of CIH on adrenal chromaffin cell secretion. Experiments were preformed on adult male mice (C57/BL6) exposed to 1‐4 days of CIH or normoxia. Perforated patch electrical capacitance recordings were preformed on freshly prepared adrenal medullary slices. Cells were directly stimulated by voltage clamp depolarization. Cells from CIH‐exposed mice exhibited a significant increase in the readily releasable pool (RRP) of secretory granules. Continuous hypoxia (CH) either for 2.5 hours (equivalent to hypoxic duration accumulated for 4 days of CIH) or for 4 days was ineffective in evoking changes in the RRP. Biochemical analysis of adrenal medullae showed both increased PKC expression and activity by CIH. PKC inhibitors prevented the CIH induced increase in RRP. CIH resulted in elevated reactive oxygen species (ROS) formation in chromaffin cells; anti‐oxidant treatment prevented ROS production, blocking the elevated RRP. These results demonstrate that CIH increases the secretory capacity in adrenal chromaffin cells at the cellular level, independent of cholinergic stimulation. Supported by NIH‐HL‐25830 and 076537 to NRP, NS‐053134 and IBN‐0344768 to CS, and BK is supported by NIH–TS HL07653.