DECREASED CATECHOLAMINE SECRETION FROM THE ADRENAL MEDULLAE OF CHRONICALLY DIABETIC BB-WISTAR RATS

Many humans with IDDM eventually lose the capacity to secrete epinephr ine from their adrenal medullae. The mechanism for this pathological c hange is unknown. We hypothesized that this abnormality is attributabl e to neuropathic changes in the greater splanchnic nerves or in the ch romaffin cells that they innervate. To study this hypothesis, we isola ted rat adrenal glands, perfused them ex vivo, and measured the epinep hrine content of the perfusate under various conditions of stimulation . We used transmural electrical stimulation (20-80 V, at 10 Hz) to ind uce epinephrine secretion indirectly by selectively activating residua l splanchnic nerve terminals within the isolated glands. Under these c onditions, epinephrine secretion was severely attenuated in glands fro m female BB-Wistar rats with diabetes of 4 mo duration compared with t heir age-matched, nondiabetic controls. These perfused diabetic adrena l medullae also demonstrated decreased catecholamine release in respon se to direct chromaffin cell depolarization with 20 mM K+, evidence th at a functional alteration exists within the chromaffin cells themselv es. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, ind icating that the secretory defect was not simply attributable to a dif ference in the amount of catecholamines stored and available for relea se. Herein, we also provide histological evidence of degenerative chan ges within the cholinergic nerve terminals that innervate these glands .