Hypoxic pulmonary vasoconstriction is unaltered by creatine depletion induced by dietary ß-guanidino propionic acid

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.