The overall objective of the proposed research project is to study the control of the pulmonary circulation by the sympathetic nervous system and humoral factors such as prostaglandins which may serve to regulate sympathetic control in the pulmonary and peripheral circulation. The effect of sympathetic stimulation on vascular resistance and release of prostaglandins will be examined in a hemodynamically separated lobe in which trauma and dissection of vessels are avoided and blood flow is maintained constant with a pump. The effect of exogenous prostaglandins and inhibition of prostaglandin biosynthesis with 5,8,11,14-tetraynoic acid, on the response of the pulmonary vascular bed to sympathetic nerve stimulation will be evaluated. The interactions between prostaglandins and the sympathetic nervous system will also be examined in the peripheral circulation. The influence of prostaglandins on responses to sympathetic nerve stimulation as well as inhibition of prostaglandin biosynthesis will be studied in the renal mesenteric, gracilis muscle and cutaneous vascular beds. The mechanisms by which prostaglandins relax or contract vascular smooth muscle, increase or decrease the responsiveness of vascular smooth muscle to adrenergic stimuli and increase or decrease the release of adrenergic neurotransmitter will be evaluated in isolated vessels on an organ to organ basis. The interactions between prostaglandins and cyclic nucleotides in vascular smooth muscle will be examined on an organ to organ basis also. Four investigators with training in the areas of peripheral circulation, pulmonary circulation, smooth muscle physiology and pharmacology, and cyclic nucleotide metabolism will integrate their efforts to achieve the objectives of the proposed research.