DECREASED ADRENAL-MEDULLARY CATECHOLAMINE RELEASE IN SPONTANEOUSLY DIABETIC BB-WISTAR RATS - ROLE OF HYPOGLYCEMIA

We have demonstrated previously that spontaneously diabetic BB-Wistar rats exhibit decreased adrenal medullary catecholamine secretion in re sponse to splanchnic nerve terminal stimulation. mie hypothesized that this abnormality is caused by changes in the sensitivity of the adren omedullary chromaffin cells to acetylcholine (ACh). To study this hypo thesis, we isolated adrenal glands hom control and spontaneously diabe tic BB-Wistar rats, perfused them with ACh, and measured catecholamine secretion. Adrenal catecholamine release in response to ACh was signi ficantly decreased at 2, 8, and 16 weeks after the onset of diabetes c ompared with age-matched, nondiabetic control rats. Catecholamine rele ase in response to perfusion with 20 mM K+ was the same in adrenals ho m diabetic and control rats. The decreased responsiveness of diabetic rat adrenals to perfusion with ACh was significantly correlated with a decrease in the release of catecholamines in response to splanchnic n erve stimulation. A similar defect in catecholamine secretion was also seen in adrenals harvested from nondiabetic BB-Wistar rats following a 3-h period of acute hypoglycemia; however, the adrenal response to p otassium was also decreased as was the catecholamine content of the ad renal. Conversely, nondiabetic BB-Wistar rats made diabetic with strep tozocin (Sn) and maintained in a hyperglycemic state did not exhibit c atecholamine hyposecretion 2 weeks after STZ administration. Collectiv ely, the data describe decreased adrenomedullary response to cholinerg ic stimulation in spontaneously diabetic rats as early as 2 weeks afte r the onset of diabetes and that a similar, although more severe, hypo secretion occurs after acute, severe hypoglycemia.