It has been suggested that a specific phosphagen pool might serve a sensor function, allowing direct detection of alveolar hypoxia by the pulmonary vascular smooth muscle. The possibility that phosphocreatine (PCr) levels could serve as such a sensor was assessed in isolated rat lungs. Pulmonary vascular reactivity to angiotensin II and alveolar hypoxia was assessed in lungs from control and PCr-depleted rats. PCr depletion was accomplished by feeding rats a diet containing 2% ß-guanidino propionic acid (ß-GPA), an competitive inhibitor of creatine uptake. Total creatine was depleted in ß-GPA lungs, compared to control lungs (p < 0.05). Lung PCr levels were undetectable by the available 31 P NMR spectroscopy system. PCr and creatine were depleted in hearts from ß-GPA rats relative to control hearts (p < 0.001). Normoxic pulmonary artery pressure and the pressor responses to angiotensin II and hypoxia were not qualitatively or quantitatively altered by the diet indicating either that PCr is not a critical participant in hypoxic pulmonary vasoconstriction or that the degree of PCr depletion achieved was inadequate to expose its role in the hypoxic pressor response.
Bibliographical noteFunding Information:
This work was supported by the Veterans Administration and NIH grants ROl HL33600 & 1 KO4-HL01241. Dr. Archer was a fellow of the Canadian Heart Foundation and the American College of Chest Physicians at the time this work was performed and is currently supported by a VA RAG grant.