Endogenous inhibitor of angiotensin converting enzyme in the rat heart.

We have identified a substance in the rat heart which inhibits ACE. This substance was characterized to be a sulfhydryl (SH) protein, the SH moiety being essential for the inhibitory activity. The inhibitory activity disappeared when the extract was boiled, or the ultrafiltrate(mol.wt.less than 10,000) was used, or when the extract was pretreated with the SH-blocking agent 5,5'-dithiobis-(2-nitro benzoic acid) at 0.5mM or the SH oxidizing agent diamide at 1mM. This substance was fractionated with Thiopropyl Sepharose affinity chromatography, precipitation with 40% ammonium sulfate saturation and high performance liquid chromatography. The mode of inhibition was competitive. In the presence of 20 micrograms/ml of this substance, the contraction of rat aortic strips induced by 5 x 10(-8)M ANG I was inhibited by 60%. This endogenous inhibitor of ACE may modulate the activity of ACE in the heart, in response to alterations in the oxidation-reduction balance in the tissue.