Hepatic and pulmonary clearance of exogenous vasoactive intestinal peptide in the rat.

1125-labeled vasoactive intestinal peptide (VIP) has been injected into the portal and systemic circulations of rats in an attempt to identify the distribution and fate of the circulating peptide. When VIP I125 was introduced into the portal circulation radioactivity was concentrated in the liver (415.5% +/- 57.2 at 10 min--counts per minute (cpm) per gram of tissue as percentage cpm per milliliter of plasma). Radioactivity in kidney and lung was 346.6% +/- 37.4 and 136.4% +/- 11.4, respectively. In contrast, if the liver was bypassed by performing a portacaval shunt or by injecting into the inferior vena cava, radioactivity was maximal in the lung (2,454.3% +/- 302.3 10 min after IVC injection) with activity in the liver of only 89.3% +/- 10.6. Analysis of the pattern of radioactivity in plasma and tissue extracts by gel filtration chromatography showed the presence of a number of fragments of smaller molecular weight than VIP with a progressive diminution of the amount of VIP-like radioactivity. Both liver and lung have the capacity to concentrate VIP from the circulation. Vasoactive intestinal peptide released into the portal circulation is probably taken up initially by the liver, and this may prevent subsequent uptake by pulmonary tissue. There is some evidence to suggest that the liver and the lung may handle VIP in different ways. If this is so, the enhanced pulmonary extraction of VIP when the liver is bypassed may have some significance for the cardiovascular complications of fulminant liver failure.