Prostaglandin E1 (PGE1) attenuates vasoconstriction induced by PGE2, PGD2 and phorbol myristate acetate in the perfused rat liver

It has been shown that prostaglandins (PGs) produced by Kupffer and endothelial cells play an important role in mediating physiological responses to various immunological stimuli. We studied the effect of prostaglandin E₁ (PGE₁) on the hemodynamic and metabolic changes induced by prostaglandin E₂ (PGE₂), D₂ (PGD₂) and phorbol 12-myristate 13-acetate (PMA), a potent inducer of PGs in the isolated rat liver perfused with Krebs-Ringer-bicarbonate (KRB) solution at a constant pressure of 12cmH₂O. The liver was taken from overnight-fasted male Sprague-Dawley rats weighing 260 to 310g. Both PGE₂ and PGD₂ significantly decreased hepatic flow when their initial concentration was elevated to micromolar range. Although 1 × 10^–6M of PGE₁ did not have a major effect on hepatic flow, it significantly attenuated the declines of hepatic flow produced by 4 × 10^–6M of PGE₂ and PGD₂. However, none of PGs tested influenced glucose and lactate concentrations in the medium. Continuous infusion of PGE₁ into the medium at a rate of 5µg·min^–1 significantly diminished the decreases in hepatic flow and oxygen consumption induced by 2 × 10^–8M of PMA. These results suggest that administration of PGE₁ may preserve hepatic blood flow by modifying the intrahepatic regulatory mechanism involving the activation of Kupffer and endothelial cells.(Inaba H, Araki M, Numai T, et al.: Prostaglandin E₁ (PGE₁) attenuates vasoconstriction induced by PGE₂, PGD₂ and phorbol myristate acetate in the perfused rat liver. J Anesth 7: 56–65, 1993)