MODULATORY EFFECTS OF ENDOGENOUS ADENOSINE ON EPINEPHRINE SECRETION FROM THE ADRENAL-MEDULLA OF THE RAT

The purpose of this study was to examine (1) whether endogenous adenos ine receptors inhibit the release of epinephrine and norepinephrine fr om adrenal medulla in response to physiological and pharmacological st imuli and (2) whether the renin-angiotensin system modulates this effe ct of endogenous adenosine. We used a conscious animal model to approx imate normal physiological conditions. Male Sprague-Dawley rats were t reated with a surface adenosine receptor antagonist, 1,3-dipropyl-8-(p -sulfophenyl)xanthine (DPSPX) to explore the effect of endogenous aden osine. Plasma epinephrine and norepinephrine levels in response to hyd ralazine-induced hypotension were measured in these animals. The same protocol was repeated in rats pretreated with either adrenalectomy or captopril. The results showed that DPSPX treatment significantly incre ased plasma epinephrine and norepinephrine levels at both baseline con ditions and after hydralazine-induced hypotension. The results from th e adrenalectomized rats showed that the difference in plasma epinephri ne level between the control and DPSPX groups originated from the adre nal medulla. Pretreatment with captopril attenuated the rise of plasma epinephrine and norepinephrine levels in DPSPX-treated animals. This result suggests that endogenous adenosine receptors inhibit epinephrin e release from the adrenal medulla and suppress plasma norepinephrine levels. When catecholamine release was stimulated by physiological and pharmacological stimuli, this inhibitory function of adenosine recept ors was augmented. The renin-angiotensin system is at least partially responsible for the modulatory function of endogenous adenosine on the catecholamine response as demonstrated in this study.