BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) is unique to pulmonary circulation. Recent hypotheses have emerged indicating that O2 levels per se can regulate ion channel activity. The modulation of both cation channels differs according to the conduit or resistance pulmonary vessel type. However, it is not yet studied that the cation channel blocker has the same effect in an animal experimental model, which can exclude several factors that may influence on HPV. The purpose of the present study was, therefore, to determine the effect of nonspecific cation blocker, Gadolinium, on HPV in a rabbit model of isolated lung perfusion. METHODS: In adult white rabbits (n = 6), lungs were isolated and perfused with the constant pulmonary perfusate flow. Acid-base status and electrolytes of perfusate also constantly maintained. Thirty minutes after, baseline hypoxic pulmonary vasoconstriction (HPV) was measured as the difference of pulmonary artery pressure between a period of 21% normoxic gas inhalation and that of 3% hypoxic gas inhalation. After another thirty minutes, Gadolinium 50microgram were mixed to the perfusate, and then HPV were measured three times. After then Gadolinium 100, 200, 400microgram were mixed to the perfusate and HPV were measured. RESULTS: Gadolinium decreased the HPV response according to the dose. The ED50 of the response was 143microgram/100 ml. CONCLUSIONS: The regulation of HPV is based on the cation channel in the isolated rabbit lung.