A novel cardiac catheterization technique was devised to investigate the pulmonary arterial pressure-blood flow relationship in intact spontaneously breathing rats (ISBR) under physiological conditions with constant left atrial pressure and controlled blood flow within the normal range. Observations using this new technique in vivo were contrasted with data derived with isolated perfused rat lungs in vitro. Unlike results in in vitro isolated perfused rat lungs, the pressure-flow curves in vivo were curvilinear, with pulmonary artery pressure increasing more rapidly at low pulmonary blood flows of 4–8 ml/min and less rapidly at higher flow rates. Pressure-flow curves were reproducible and were not altered by 1–1.5 h of arrested perfusion, cyclooxygenase blockade, or perfusion with aortic or mixed venous blood. In contrast to results in in vitro isolated perfused rat lungs, N G-nitro-l-arginine methyl ester (l-NAME) increased pulmonary arterial pressure at all but the lowest flow rates with a slight effect on the curvilinear pressure-flow relationship. l-NAME reversed pulmonary vasodilator responses to acetylcholine and bradykinin and enhanced the pulmonary vasodilator response to nitroglycerin. The present data suggest that actively induced pulmonary hypertension is under greater control by endothelium-derived relaxing factor (EDRF). Unlike previous results in in vitro perfused rat lungs, results in ISBR demonstrate that the pulmonary vasodilator response to adrenomedullin-(13—52) is not mediated by calcitonin gene-related peptide receptors, which are not coupled to the release of EDRF. These results indicate that this novel technique may provide a useful model for the study of the pulmonary circulation in the intact chest rat.
The present study employed a new right-heart catheterization technique to measure pulmonary arterial pressure, pulmonary arterial wedge pressure, and pulmonary vascular resistance in anesthetized intact-chest, spontaneously breathing mice. Under fluoroscopic guidance, a specially designed catheter was inserted via the right jugular vein and advanced to the main pulmonary artery. Cardiac output was determined by the thermodilution technique, and measured parameters were stable for periods of =3 h. Pressure-flow curves in vivo were curvilinear, with mean pulmonary arterial pressure increasing more rapidly at low pulmonary blood flows of 5-10 ml/min and less rapidly at higher blood flow rates. The pressure-flow relationship was shifted to the left by the nitric oxide synthase inhibitor nitro-L-arginine methyl ester (L-NAME) at higher blood flow levels, whereas the cyclooxygenase inhibitor sodium meclofenamate was without effect. The increase in pulmonary arterial pressure in response to acute hypoxia (fractional inspired O(2) 10%) was augmented by L-NAME but unaltered by sodium meclofenamate. The present results demonstrate that the right-heart catheterization technique can be used to measure pulmonary vascular pressures and responses in the mouse. This is, to our knowledge, the first report of a right-heart catheterization technique to measure pulmonary vascular pressures and responses in the intact-chest, spontaneously breathing mouse and should prove useful for the investigation of pulmonary vascular responses in transgenic mice.
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