The candidate received residency training in both Internal Medicine and Anesthesiology, and subspecialty training in Critical Care Medicine, and joined the faculty of Johns Hopkins Hospital 3 years ago as Associate Director of the Surgical Intensive Care Unit. In addition to administrative, patient care and teaching activities, the candidate has participated in physiology research projects investigating adrenal blood flow regulation, and regional perfusion during endotoxin shock. This work resulted in development of a radiolabelled microsphere technique for separate measurement of adrenal medullary and cortical blood flow. Data obtained with this technique indicate that blood flow to the medulla and cortex may be independently regulated, and that stimuli which elicit medullary and cortex secretory activity are associated with vasodilation, particularly in medulla where blood flow increases several-fold even during hemorrhagic hypotension. No other organ is known to demonstrate increased blood flow with reduction of arterial blood pressure, and investigation into mechanisms responsible for this marked vasodilation will constitute the first Specific Aim of the Research Plan. In these experiments the effect of muscarinic, nicotinic, adrenergic and adenosine receptor antagonists on nerve stimulation-induced medullary vasodilation, will be used to differentiate neurotransmitter mediated vasodilation from chromaffin granule content-mediated vasodilation. In Specific Aim 2, potential physiologic implications of increased medullary blood flow during catecholamine secretion will be investigated. Experiments to determine whether increased medullary blood flow is necessary for maximal catecholamine secretion will be performed, and mechanisms of blood flow effects on catecholamine secretion will be evaluated. Specific Aim 3 will determine whether cortical blood flow increases during cortisol synthesis and secretion, using exogenously administered ACTH as an adrenocortical activator. Specific inhibitors of cortisol synthesis will be used to determine whether ACTH-induced cortical vasodilation is coupled with cortical synthetic activity. Little is known concerning regulation of blood flow and metabolism in endocrine tissues, and the studies outlined in this grant proposal should provide new insights into the physiology of these two important endocrine organs.