GLUCOCORTICOIDS, SYMPATHETIC ACTIVITY, AND PRESYNAPTIC ALPHA(2)-ADRENOCEPTOR FUNCTION IN HUMANS

The sympathetic nervous system and the pituitary-adrenocortical system are two of the body's main stress effector systems. Animal studies ha ve indicated that exogenously administered glucocorticoids inhibit sym pathetic outflows and interfere with the function of presynaptic alpha (2)-adrenoceptors modulating neuronal norepinephrine (NE) release. The present study tested whether glucocorticoids produce similar effects in humans. In a randomized, double-blind, placebo-controlled cross-ove r experiment, 15 healthy subjects took 20 mg prednisone or placebo ora lly daily each morning for 1 week, followed by the other drug after a 1-week washout. On the last day of each treatment week, blood samples were drawn for assays of plasma levels of catechols and ACTH before an d after iv infusion of the alpha(2)-adrenoceptor antagonist yohimbine (YOH) (0.125 mg/kg bolus, 0.001 mg . kg(-)1 . min(-1) infusion). In 7 subjects, directly recorded peroneal skeletal muscle sympathetic nerve activity (MSNA) was also measured at baseline and after YOH infusion at the end of both treatment weeks. Prednisone decreased plasma NE lev els and MSNA compared with levels after placebo (1.09 +/- 0.11 nmol/L US. 1.40 +/- 0.13 nmol/L, P < 0.01; 30 +/- 4 bursts/min us. 36 +/- 3 b ursts/min, P < 0.05) without affecting blood pressure or pulse rate. Y OH increased mean arterial blood pressure by 12% (P < 0.001) and heart rate by 7% (P < 0.05); prednisone did not alter these effects of YOH. YOH-induced proportionate increments in plasma NE levels averaged abo ut 10 times those in MSNA. Prednisone did not affect the YOH-induced p roportionate increments in plasma NE levels (placebo, 243%; prednisone , 237%) or MSNA (placebo, 22%; prednisone, 23%). The decrements in MSN A and plasma NE levels after prednisone treatment indicate that glucoc orticoids inhibit sympathoneural outflows in humans. The 10-fold large r NE than MSNA response to YOH confirms substantial inhibitory modulat ion of NE release by alpha(2)-adrenoceptors on noradrenergic terminals , and the similarity of responses to YOH after prednisone or placebo s uggests that glucocorticoid-induced sympathoinhibition occurs independ ently of altered modulatory function of alpha(2)-adrenoceptors on nora drenergic terminals.