Hemorrhage alters plasma and cardiac enkephalins and catecholamines in anesthetized dogs

Intrinsic cardiac enkephalins participate in circulatory regulation either through the modification of vagal control or vasomotor sympathetic control. We extracted, chromatographed, and assayed plasma and myocardial enkephalins from anesthetized dogs under control conditions and during hemorrhagic hypotension (2 h at 40 mmHg). Blood samples were collected at intervals during the experiment. Blood gases were stable, pH declined to 7.1, and heart rate rose. Plasma catecholamines increased and remained high throughout hypotension. Catecholamine and enkephalin immunoreactivities (ir) were unchanged in time controls. Plasma methionine-enkephalin (ME) and peptide F increased twofold and methionine-enkephalin-arginine-phenylalanine (MEAP) and peptide B increased 10- to 30-fold during hypotension. Plasma proenkephalin (ProEnk) and other large enkephalins were unchanged during hypotension. Myocardial norepinephrine was greater in the atria and both atrial and ventricular contents were decreased after hypotension. ProEnk and peptide B accounted for > 60% of the cardiac enkephalins, and their ventricular concentrations were three to four times atrial concentrations. Myocardial MEAP concentrations were 15-25 times the ME concentrations in the same tissue extracts. Hypotension increased myocardial peptide B and ProEnk, and ME, MEAP, and peptide F were unchanged. The data demonstrate a preferential processing to or retention of MEAP rather than ME-ir enkephalins in the heart. The data also indicate that myocardial MEAP-ir enkephalins respond to changes in the circulatory environment and appear in the plasma during hemorrhagic hypotension.