Bronchial asthma and pulmonary hypertension are diseases which may involve changes in the contractile state of smooth muscle in intrapulmonary vessels and airways. However, effective treatment of these diseases requires fundamental knowledge concerning morphology, physiology and pharmacology of the airway and pulmonary vascular smooth muscle. The objective of the proposed research is to improve our knowledge of the regulation of intrapulmonary vessels and airways by hormonal factors such as prostaglandins, peptides and vasoactive amines. In order to accomplish this objective, helical segments of large and small airways and of intrapulmonary artery and vein will be removed from the lungs of several laboratory species. The helical segments will be mounted in an isolated organ bath in which temperature, pH, PO2, PCO2 and resting load can be carefully controlled and changes in isometric force generation recorded on a polygraph. The effects of prostaglandins, prostacyclins, and thromboxanes on isometric force output will be studied in intrapulmonary vessels and airways. Furthermore, the effects of a number of vasoactive hormones and drugs which may be useful in treating pulmonary hypertension and bronchial asthma will be assessed. In addition, studies will be undertaken to identify the pools of calcium utilized for postaglandin induced contraction. The final objectives of this proposal are to investigate calcium metabolism by subcellular organelles and to identify the source of activator calcium in pulmonary vascular and airway smooth muscle. Changes in bronchomotor activity in the intact animal will be correlated with changes in contractile activity in intrapulmonary airways. Results of these studies may lead to new modes of therapy for pulmonary hypertension and bronchial asthma.