(Circulation. 1998;98:73-81.)
© 1998 American Heart Association, Inc.
Basic Science Reports |
Angiotensin Production by the Heart
A Quantitative Study in Pigs With the Use of Radiolabeled Angiotensin Infusions
From the Departments of Internal Medicine (J.P.v.K., M.A.D.H.S.), Experimental Cardiology (J.P.v.K., J.R.v.M., L.M.A.S., P.D.V.), and Pharmacology (A.H.J.D.), Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), the Netherlands.
Correspondence to A.H.J. Danser, PhD, Department of Pharmacology, Room EE 1418 B, Erasmus University Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, Netherlands. E-mail danser{at}farma.fgg.eur.nl
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.
Key Words: angiotensin • ACE inhibitors • renin
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