Aortic perfusion pressure as a determinant of cardiac protein synthesis.
Mechanical parameters and intracellular mediators that may control protein synthesis have been studied in isolated rat hearts subjected to increased aortic pressure or induced to perform cardiac work. Elevation of aortic pressure from 60 to 120 mmHg in Langendorff preparations with glucose, glucose plus insulin, or pyruvate raised the rate of protein synthesis during the 2nd h of perfusion. These effects involved faster rates of both peptide chain initiation and elongation. In working hearts supplied glucose or glucose plus insulin, higher rate of synthesis were observed in both the 1st and 2nd h of perfusion, compared with Langendorff preparations perfused at 60 mmHg. Intracellular levels of glucose 6-phosphate, ATP/ADP ratio, adenylate energy charge, or creatine phosphate/creatine did not correlate with the rate of protein synthesis in beating control hearts. When ventricular pressure development was prevented by ventricular draining and hearts were arrested with tetrodotoxin, protein synthesis still increased as a function of perfusion pressure. Oxygen consumption increased as aortic pressure was raised in beating-drained hearts but was unaffected in arrested-drained hearts. These results indicate that intraventricular pressure development, cardiac contraction, oxygen consumption, glucose 6-phosphate, energy availability, and coronary flow could be dissociated from the stimulatory effect of higher aortic pressures on protein synthesis and suggested that stretch of the ventricular wall, as a consequence of increased aortic pressure, could be the mechanical parameter most closely related to the increase in protein synthesis.
D000818:Animals; D001011:Aorta / Q000502:physiology*; D004734:Energy Metabolism; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000032:analysis; D006339:Heart Rate; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D009206:Myocardium / Q000032:analysis / Q000378:metabolism*; D010477:Perfusion; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains
D005958:Glucosephosphates; D009124:Muscle Proteins; D019298:Glucose-6-Phosphate