The 1995 Ciba-Geigy Award Lecture. Intrinsic regulation of hepatic blood flow.

Intrinsic regulation of hepatic blood flow is mediated only through the hepatic artery because the liver is not able to directly regulate portal vein blood flow. Hepatic metabolic activity does not affect hepatic artery flow. Although the hepatic artery is affected by sympathetic nerves and blood-borne agents, the intrinsic regulation of the hepatic artery can be demonstrated if these factors are controlled. The primary intrinsic regulator of the hepatic artery is the hepatic arterial buffer response, which is the inverse response of the hepatic artery to changes in portal vein flow. The hepatic arterial buffer response is sufficiently powerful that doubling portal vein flow leads to maximal constriction in the hepatic artery, while low portal vein flow can result in maximal dilation. The mechanism of the hepatic arterial buffer response is based on adenosine washout, whereby adenosine is produced at a constant rate, independent of oxygen supply or demand, and secreted into a small fluid compartment that surrounds the hepatic arterial resistance vessels. If portal vein flow decreases, less adenosine is washed away into the portal blood and the accumulated adenosine leads to hepatic arterial dilation. Similarly, hepatic arterial autoregulation operates by the same mechanism, whereby a decrease in arterial pressure leads to a decrease in hepatic arterial flow, thus resulting in less adenosine washout into the hepatic artery blood. The accumulated adenosine leads to hepatic artery dilation. These intrinsic regulatory mechanisms tend to maintain total hepatic blood flow at a constant level, thus stabilizing hepatic clearance of hormones, venous return, and cardiac output.