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The distribution of atrial natriuretic peptide (ANP) clearance receptors in rat kidney was investigated by in vitro autoradiography using des[Gln18,Ser19,Gly20,Leu21,Gly22]-ANP-(4- 23) (C-ANP) and 125I-Tyr0-ANP-(5-25) as relatively specific ligands of this receptor. Alpha-125I-ANP (100 pM) bound reversibly but with high affinity to glomeruli, outer medullary vasa recta bundles, and inner medulla. C-ANP (10 microM) inhibited greater than 60% of this glomerular binding but did not inhibit the binding of alpha-125I-ANP to medullary tissues. Alpha-125I-ANP also bound reversibly to the renal arteries up to the glomerulus. This arterial binding was only partly inhibited by 10 microM C-ANP. In the presence of 10 microM C-ANP, increasing concentrations of alpha-125I-ANP bound to a residue of glomerular sites with apparent dissociation constants of 0.82 +/- 0.16 to 2.73 +/- 1.20 nM at different cortical levels. 125I-Tyr0-ANP-(5-25) bound significantly to glomeruli and intrarenal arteries but not to vasa recta bundles or inner medulla. This glomerular binding also occurred with nanomolar dissociation constants. It was completely inhibited by 1 microM alpha-ANP and 10 microM C-ANP, but not by unrelated peptides such as gastrin. These results suggest that renal ANP clearance receptors are restricted in vivo to the glomeruli and renal arterial system of the rat.

Effects of changes in pulmonary arterial (Pa), venous (Pv), and alveolar (Pa) pressures on the over-all pressure-blood flow relations of an isolated dog lung have been re-examined. In the preparation used, the distribution of blood flow was predictable from previous measurements with radioactive gases. The results showed that the pressure-flow relations of the whole lung were greatly affected by the distribution of blood flow within it. For example, the pulmonary vascular resistance (PVR) of the lung depended on whether all the lung was perfused with blood or not, and thus whether there was an unperfused zone at the top of the lung where Pa was less than Pa ( zone 1). Again the pressure-flow relations of the lung were shown to depend on how much of the lung had a Pv less than Pa ( zone 2), and how much had a Pv which exceeded Pa ( zone 3). The effects on PVR of changing Pv or Pa could be explained on this basis. No evidence of a critical closing pressure in the vessels of the expanded lung was found. It was concluded that although the over-all pressure-flow relations of the whole lung were complicated, the flow through individual vessels could be accounted for by the simple mechanical effects of pressures inside and outside the vessels. hydrostatic effect; pulmonary vascular resistance; Starling resistor; vascular waterfall; critical closing pressure Submitted on May 4, 1964

Carbon dioxide labeled with oxygen 15 has been used to measure regional blood flow in the lung by counting over the chest during a short breath-holding period following a single breath of the gas. This gas has been found to exhibit different physiological behavior from carbon-11-labeled CO2. For example, the clearance rates of the oxygen-labeled gas are about twice as fast as those of carbon-labeled CO2. Measurements on alveolar gas expired immediately after inspiration of active gas show that the oxygen-labeled gas disappears from the alveoli about ten times faster than its carbon-labeled counterpart. In addition, if venous blood is drawn shortly after a breath of oxygen-labeled CO2, the activity cannot be removed from the blood by adding acid and shaking under vacuum, whereas the expected loss of activity occurs for carbon-labeled gas. These apparent discrepancies can be explained by exchange between the oxygen atoms of water and bicarbonate after the gas has been taken up by the blood. In vitro measurements show that the uptake of oxygen-labeled CO2 into blood can be reduced by adding carbonic anhydrase inhibitor. The results affect the interpretation of the clearance rates of other radioactive gases in the lung. Submitted on December 7, 1960

The airways of degassed greyhound lungs were filled with saline and the lung suspended in a saline bath and perfused with blood. The distribution of blood flow was measured by injecting aggregated I131-labeled albumin into the pulmonary artery and scanning the lung from bottom to top when the particles had been trapped by the small vessels. After equilibrating the alveolar saline with more inhaled iodinated albumin and scanning again, blood flow per unit alveolar volume could be calculated. With vascular pressures which have been shown to cause great topographical inequality of blood flow in the gas-filled lung, blood flow was evenly distributed on the average in the saline-filled preparation, presumably because the hydrostatic pressures difference in the blood vessels were balanced by corresponding pressures in the airways. The topographical distribution of a single breath of iodinated albumin in saline was found to be uniform but there was striking stratified inhomogeneity along the airways. This was due to the slow diffusion rate of albumin in saline and similar effects were seen with inhaled radioactive oxygen and carbon dioxide dissolved in saline. The results show that when the mammalian lung breathes saline, diffusion limitations for oxygen and carbon dioxide within the airways may be an important factor. aerosols; hydrostatic pressures; increased acceleration; airways diffusion; topographical differences; gas exchange; pressure-flow relations Submitted on March 18, 1965

Inhaled radioactive CO2 is rapidly taken up by pulmonary blood. By external counting over the chest during breath holding, the clearance rate of radioactive CO2xs from the counting field can be recorded, and is proportional to the regional perfusion. In normal subjects, the clearance rate varied from about 20%/ sec. at the base of the lung to virtually nil at the apex, and the change was approximately linear with distance up the chest. The difference between upper and lower zones was reduced on moderate exercise and eliminated when the subject lay on his back. By relating the counting rate at the end of inspiration to the volume of lung in the counting field, the difference in ventilation between upper and lower zones was measured and found to be small. Variation in ventilation-perfusion ratio was thus determined. Alveolar-arterial O2 gradient expected from this ventilation-perfusion ratio inequality was calculated to be about 4 mm Hg. This suggests that the variation in blood flow between upper and lower parts of the lung in erect man accounts for the whole of the ventilation-perfusion ratio inequality in the normal lung. Submitted on November 23, 1959

Carbon monoxide labeling with O15 was produced by passing O15, made in the Medical Research Council's cyclotron, over charcoal at 1000° C. After a single breath of the radioactive gas the rate of fall of activity during apnea was measured by external counting in different regions of the lungs of normal subjects in the sitting position. The carbon monoxide ‘clearance rate’ calculated from these data is proportional to the diffusion per unit volume in the zone under study. There was a gradient of diffusion per unit volume, the highest value being found in the basal regions of the lung and much lower values toward the apex. On exercise the clearance rate in the upper zone increased to a value similar to that in the lower zone at rest; the clearance rate in the lower zone was unchanged. Measurements of the O15clearance rate showed a similar gradient but on exercise both upper and lower zone values increased so that the gradient was maintained. The results are interpreted as showing that in the resting state all the basal capillaries are open but that the proportion of patent capillaries diminishes toward the apex. On exercise there is an increase in flow at both apex and base and in consequence the remaining apical capillaries open. Submitted on December 21, 1959