Increased Portal Venous Resistance Hinders Portal Pressure Reduction During the Administration of β–Adrenergic Blocking Agents in A Portal Hypertensive Model

Abstract

We have recently shown that maintenance of portal hypertension in rats is highly dependent on high portal blood flow. This study attempts to determine whether portal hypertension, induced in the rat by partial constriction of the portal vein, can be reduced by lowering portal blood flow with a beta blocking agent. Portal hypertensive rats treated with propranolol had a reduction in portal blood flow to 0.89 ± 0.13 ml · min^-1 · gm^-1 accompanied by reduction in portal pressure to 12.6 ± 1.00 mm Hg, disproportionately small because of a rise in portal–collateral vascular resistance to 12.52 ± 1.63 dyne · sec · cm^-5 · gm · 10⁵ accompanying the portal blood flow reduction. Similarly, portal hypertensive rats receiving β–blockade with H35-25, an experimental β–blocker, demonstrated a 49% reduction in portal blood flow accompanied by only a 14% reduction in portal pressure, also disproportionately low because of a complicating 77% rise in portal–collateral vascular resistance. Normal rats were then given saline infusion to achieve similar blood flow elevations to that of portal hypertensive animals. Within a similar portal blood flow range of 0.76 ± 0.14 to 1.31 ± 0.07 ml · min^-1 · gm^-1, Portal hypertensive animals exhibited a significantly higher portal pressure range (12.6 ± 1.0 to 15.4 ± 0.4 mm Hg) than normals (8.9 ± 0.4 to 9.5 ± 0.4 mm Hg) largely due to a significantly higher range of portal resistance offered to portal blood flow by the portal–collateral bed of portal hypertensive rats (9.39 ± 0.25 to 16.63 ± 1.45 dyne · sec · cm^-5 · gm · 10⁵) in comparison with the portal venous system of normal animals (5.47 ± 0.70 to 10.00 ± 0.43 dyne · sec · cm^-5 · gm · 10⁵). We conclude that, in a hyperdynamic model of portal hypertension, the increase in portal pressure appears to be the result of combined elevations in portal blood flow and the portal vascular resistance to that flow. β–Blockade completely corrects the portal blood flow factor, but will be unable to adequately reduce portal pressure until the additional element of elevated portal vascular resistance can also be reduced.