ABSTRACT
This study evaluated the effects of PKC activation using phorbol 12-myristate 13-acetate (PMA) and PKC inhibition using the isoquinoline sulfomide derivative H-7 on hemodynamics and glucoregulation in the isolated perfused rat liver. Livers were isolated from fed male Holtzman rats and perfused with Krebs Ringer bicarbonate solution under a constant flow of 50 ml/min at 35degreeC. Portal vein pressure, glucose and lactate concentrations in the medium and oxygen consumption rates were continuously monitored by a Grass polygraph, YSI glucose and lactate monitors, and a YSI oxygen monitor, respectively. PMA at concentration of 2 to 200 nM increased the portal vein pressure, glucose and lactate production, but decreased oxygen consumption rate in a dose-dependent fashion. H-7 (200 micrometer) attenuated PMA (50 nM)-induced vasoconstriction (15.1+/-1.36 vs 10.56+/-1.17 mmHg), glucose production rate (91.3+/-6.15 vs 71.8+/-2.50 micromoles/g/hr), lactate production rate (72.4+/-6.82 vs 53.6+/-4.82 micromoles/g/hr) and oxygen consumption rate (33.7+/-1.41 vs 27.9+/-1.75 microliter/g/min). The effects of PMA were blocked either by addition of verapamil (9 micrometer) or perfusion with Ca2+-free KRB. These results suggest that the hemodynamic and glucoregulatory changes in the perfused rat liver are mediated by protein kinase C activation and require Ca2+ influx from the extracellular fluid.