Physiological features of edematous dogs unresponsive to atrial natriuretic peptide

Sodium-retaining cirrhotic and chronic caval dogs with ascites show a heterogeneous natriuretic response to atrial natriuretic factor (ANF) infusions such that half will increase their urinary excretion of sodium and half will show no natriuretic response whatsoever. In these studies we have examined several physiological variables that might discriminate between these two experimental populations. We studied 22 caval dogs (11 natriuretic responders, 11 nonresponders) and 19 cirrhotic dogs (9 responders, 10 nonresponders). After an infusion of rat ANP-(1-28), 125 ng.kg-1.min-1, differences in glomerular filtration rate, blood pressure, or urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP) could not differentiate between the two types of dogs. When the left kidney of nonresponding dogs in both the caval and cirrhotic groups was either denervated or vasodilated with acetylcholine bromide (60-80 micrograms/min), the attenuation of the natriuretic response to ANF was not reversed. Papillary plasma flow (PPF) after ANF infusion was measured by a Lillienfield technique and averaged 36 +/- 4 ml.min-1.100 g-1 in normal dogs, 10.7 +/- 0.7 ml.min-1.100 g-1 in both responding and nonresponding caval dogs, and 48.3 +/- 1.1 ml.min-1.100 g-1 for each group of cirrhotic dogs. We conclude that differences in renal perfusion, PPF, cGMP generation, or the presence of intact renal nerves cannot explain the lack of a post-ANF natriuretic response in half of caval or cirrhotic dogs. Other physiological determinants must explain the heterogeneity of natriuretic response to ANF observed in edematous dogs.