GLUCOCORTICOID-INDUCED SYMPATHOINHIBITION IN HUMANS

Objective: To test whether glucocorticoids inhibit sympathetic nerve a ctivity or norepinephrine release in humans, as has been suggested by results in laboratory animals. Methods: This was a double-blind, place bo-controlled, randomized crossover study performed at the Clinical Ce nter of the National Institutes of Health. Thirteen normal volunteers received 20 mg prednisone or placebo orally each morning for 1 week, f ollowed by a washout period of 1 week and then by treatment with the o ther drug for 1 week On the last day of each treatment week, blood sam ples were drawn for measurements of plasma levels of catecholamines an d their metabolites, of cortisol, and of corticotropin at baseline and during reflexive sympathetic stimulation elicited by lower body negat ive pressure (-15 mm Hg). A 24-hour urine collection was obtained at t he end of each week of treatment for measurement of urinary excretion of catechols. In eight subjects, directly recorded peroneal skeletal m uscle sympathetic nerve activity was also measured after both treatmen ts. Results: Prednisone significantly decreased sympathetic nerve acti vity by 23% +/- 6%, plasma norepinephrine levels by 27% +/- 6%, and pl asma corticotropin levels by 77%. Blood pressure, heart rate, body wei ght, and urinary excretion of catechols and electrolytes were unaffect ed. Prednisone did not alter proportionate increments in sympathetic n erve activity or plasma norepinephrine levels during lower body negati ve pressure. Relationships between sympathetic nerve activity and plas ma norepinephrine levels were unchanged. Conclusion: Glucocorticoids d ecrease sympathoneural outflows in humans without affecting acute symp athoneural responses to decreased cardiac filling and probably without affecting presynaptic medulation of norepinephrine release.