Contribution of the kidney to metabolic clearance of atrial natriuretic peptide

To quantify the role of the kidney in whole body metabolic clearance rate (MRC) from plasma of atrial natriuretic peptide (ANP), synthetic α-human ANP-(1-28) was infused at 200 ng/min to steady-state conditions in chronically instrumented one-kidney conscious dogs. Clearances were measured in dogs with a normally filtering kidney and they were also measured after the glomerular filtration rate (GFR) was reduced to close to zero by acutely inflating a cuff around the renal artery (RAC), which resulted in minimal urine production and renal blood flow reduction to 59% of the testing level. In normal dogs, MCR was 1,090 ± 134 ml/min with renal clearance rate (RCR) contributing only 13.9%. After RAC, MCR fell to 864 ± 151 ml/min, due in part to a fall in RCR (-41.5 ± 12.9 ml/min), but mostly due to a fall in 'rest of the body' (total renal) clearance of ANP. The reduced GFR accounted for virtually all the fall in RCR. Normal plasma ANP half-life was 59.6 ± 7.9 s. In conclusion, MCR of ANP was very high, approaching the cardiac output, suggesting that most of ANP is cleared in one circulation through peripheral tissues. GFR contributed significantly to RCR (~30%) but the contribution of the kidney to whole body MCR was small relative to rest of the body clearance of ANP.