In newborn mammals, systemic hypoxia provokes catecholamine secretion from the adrenal medulla. In contrast to adults, this release is independent of sympathetic innervation. We have studied the cellular processes involved in hypoxia‐induced catecholamine secretion, employing fluorimetric techniques to measure changes in [Ca2+]i, NADH and mitochondrial potential, and voltammetric techniques to record changes in PO2 and catecholamine secretion. In adrenal chromaffin cells freshly dissociated from newborn rats, severe hypoxia increased [Ca2+]i and secretion of catecholamines, indicating that the response of the newborn adrenal medulla to hypoxia is an intrinsic property of these cells. Discrete quantal secretory events were identifiable, suggesting an exocytotic mechanism of secretion. Hypoxia‐induced secretion was only seen when PO2fell below 5 mmHg, similar to the threshold arterial PO2 reported to stimulate release in vivo. Such oxygen tensions also inhibited mitochondrial metabolism, shown by an increase in NADH autofluorescence. We therefore explored the involvement of mitochondria in oxygen sensing. Inhibition of mitochondrial respiration either by CN− at complex IV or by rotenone at complex I mimicked severe hypoxia, reversibly increasing both [Ca2+]i and catecholamine secretion. The CN−‐induced depolarization of the mitochondrial inner membrane potential preceded the increase in [Ca2]i by ∼6 s. The effects of severe hypoxia and CN− on [Ca2+]i and catecholamine secretion were not additive, suggesting a common mechanism. Chemical anoxia failed to increase [Ca2+]i in a significant proportion of cells dissociated from 2‐ to 4‐week‐old rats. Thus, the sensitivity to hypoxia is specific to adrenal chromaffin cells dissociated from newborn rats. These data indicate that hypoxia‐induced catecholamine secretion in the newborn adrenal medulla is mediated by reversible inhibition of mitochondrial respiration, leading to an increase in [Ca2+]i and catecholamine secretion.

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The C57BL/6J (BL/6) mouse develops non-insulin-dependent diabetes mellitus (NIDDM) when fed a high fat-high simple carbohydrate (HFHSC) diet, whereas A/J mice do not. The purpose of the study was to determine whether hypertension occurred with NIDDM and whether it was sustained by sympathetic nervous system (SNS) hyperactivity. After 3 mo on an HFHSC diet with a low Na content (0.06%), awake, tail-cuff systolic blood pressure (BP) increased 20% above the control diet in BL/6 (138 +/- 3 vs. 115 +/- 4) but not in A/J (115 +/- 6 vs. 113 +/- 2 mmHg) mice. On a normal Na (0.4%)-HFHSC diet, BL/6 mice had a higher BP than on 0.06% Na (149 +/- 3 at 3 mo, 162 +/- 6 at 4.5 mo). After 1 mo on the 0.06% Na-HFHSC diet, direct BP of anesthetized BL/6 mice was 18% higher than control. The hypotensive response to interruption of SNS activity by ganglionic blockade (chlorisondamine) increased in the BL/6 mice (50%), whereas the heart rate response increased in both strains (20-30%). Analysis of variance (ANOVA) on glucose detected significant effects of strain and diet and a strain x diet interaction (P = 0.0007). At 1 or 3 mo, HFHSC-fed BL/6 mice were hyperglycemic (> 11 mM) compared with diet or strain controls. The ANOVA on insulin detected strain and diet effects but not a strain x diet interaction (P = 0.3). HFHSC increased insulin above the control of 140-160 pM in A/J and BL/6 strain (20-70% at 1 mo, 400% at 3 mo).(ABSTRACT TRUNCATED AT 250 WORDS)

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