Effects of pepstatin on reducing hypoxia-induced injury in the isolated guniea pig heart.
Intracellular cathepsin D is thought to play a role in myocardial injury produced by ischemia and hypoxia. Pepstatin, a known inhibitor of cathepsin D, was infused into isolated guniea pig hearts (Langendorff preparation) in order to observe if such an administration of pepstatin would protect against the effects of a two minute exposure to hypoxia. Hypoxia was produced by exposing the hearts to perfusion fluid aerated with 20% 02/5% CO2/75% N2 and containing 0.5 microgram/ml of norepinephrine. Contractile force, heart rate, coronary flow and ECG were monitored. Samples of heart tissue were assayed for cathepsin D activity. Infusion of 0.06 mg/min of pepstatin for 30 minutes produced no significant alterations in the parameters of cardiac function studied. However, this amount of pepstatin inhibited 97% of the cathepsin D activity of the hearts. The characteristics ECG alterations produced by hypoxia were significantly reduced after infusion of pepstatin. These data indicate that pepstatin may protect the heart against hypoxia-induced injury.
D000818:Animals; D002402:Cathepsin D; D002403:Cathepsins / Q000378:metabolism; D004562:Electrocardiography; D006168:Guinea Pigs; D006331:Heart Diseases / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology; D009842:Oligopeptides / Q000502:physiology*; D010436:Pepstatins / Q000502:physiology*
D009842:Oligopeptides; D010436:Pepstatins; C014195:Streptomyces pepsin inhibitor; D002403:Cathepsins; D002402:Cathepsin D; C031375:pepstatin