Angiotensin production by the heart: a quantitative study in pigs with the use of radiolabeled angiotensin infusions

BACKGROUND: Beneficial effects of ACE inhibitors on the heart may be mediated by decreased cardiac angiotensin II (Ang II) production. METHODS AND RESULTS: To determine whether cardiac Ang I and Ang II are produced in situ or derived from the circulation, we infused 125I-labeled Ang I or II into pigs (25 to 30 kg) and measured 125I-Ang I and II as well as endogenous Ang I and II in cardiac tissue and blood plasma. In untreated pigs, the tissue Ang II concentration (per gram wet weight) in different parts of the heart was 5 times the concentration (per milliliter) in plasma, and the tissue Ang I concentration was 75% of the plasma Ang I concentration. Tissue 125I-Ang II during 125I-Ang II infusion was 75% of 125I-Ang II in arterial plasma, whereas tissue 125I-Ang I during 125I-Ang I infusion was <4% of 125I-Ang I in arterial plasma. After treatment with the ACE inhibitor captopril (25 mg twice daily), Ang II fell in plasma but not in tissue, and Ang I and renin rose both in plasma and tissue, whereas angiotensinogen did not change in plasma and fell in tissue. Tissue 125I-Ang II derived by conversion from arterially delivered 125I-Ang I fell from 23% to <2% of 125I-Ang I in arterial plasma. CONCLUSIONS: Most of the cardiac Ang II appears to be produced at tissue sites by conversion of in situ-synthesized rather than blood-derived Ang I. Our study also indicates that under certain experimental conditions, the heart can maintain its Ang II production, whereas the production of circulating Ang II is effectively suppressed.