Aortic pressure as a determinant of cardiac protein degradation.
Mechanical parameters and intracellular mediators that may control protein degradation were studied in isolated rat hearts subjected to increased aortic pressure. Elevation of aortic pressure from 60 to 120 mmHg in Langendorff preparations provided glucose or pyruvate as substrate decreased the rate of protein degradation during the second hour of perfusion. Intracellular contents of ATP or creatine phosphate or the creatine phosphate/creatine ratio did not indicate that energy depletion accounted for these effects. When ventricular pressure development was prevented by ventricular draining, and hearts were arrested with tetrodotoxin, protein degradation still decreased as aortic pressure was raised. The effect of elevated aortic pressure on proteolysis was unchanged when perfusate calcium concentrations were 0.6, 3.0, or 5.1 mM, or when indomethacin or meclofenamate was added to the perfusion buffer. These results provided no evidence to indicate that intraventricular pressure development or cardiac contraction was responsible for the inhibitory effect of increased aortic pressure on protein degradation. Instead, they suggested that stretch of the ventricular wall, as a consequence of increased aortic pressure, could be the mechanical parameter most closely related to the restraint on proteolysis. No evidence was obtained that the lower rate of degradation depended on energy or calcium availability or prostaglandin synthesis.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011312:Pressure; D011453:Prostaglandins / Q000096:biosynthesis; D011506:Proteins / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D011453:Prostaglandins; D011506:Proteins; D011773:Pyruvates; D010725:Phosphocreatine; D013779:Tetrodotoxin; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D002118:Calcium