Angiotensin II-forming pathways in normal and failing human hearts.

TLDR

ACE inhibitors lower preload and afterload but may also reduce the beneficial myocardial contractile effects of angiotensin II. The study aimed to determine how ACE inhibition suppresses cardiac angiotensin II formation in humans. The authors measured angiotensin II–forming activity in left ventricular membrane preparations from eight normal and 24 failing hearts, assessing both ACE‑dependent and ACE‑independent pathways by converting radiolabeled angiotensin I to angiotensin II. Angiotensin II–forming activity was similar in normal and ischemic cardiomyopathy hearts but was 48 % lower in idiopathic cardiomyopathy hearts. Abstract truncated at 250 words.

Abstract

Reduced preload and afterload to the heart are important effects of angiotensin converting enzyme (ACE) inhibitors in the treatment of congestive heart failure. However, since angiotensin II (Ang II) directly increases the strength of myocardial contraction, suppression of Ang II formation by ACE inhibitors could potentially reduce the beneficial effects of Ang II on the failing heart. To study how ACE inhibition suppresses cardiac Ang II formation in man, we characterized ACE-dependent and ACE-independent Ang II-forming pathways in eight normal and 24 failing human hearts obtained at cardiac transplantation. Ang II-forming activity in left ventricular (LV) membrane preparations was assessed by measuring the conversion of [125I]angiotensin I (Ang I) to [125I]Ang II. LV [125I]Ang II-forming activity in normal hearts (35.5 +/- 2.7 fmol/min/mg, n = 8) was not different from that in hearts from patients with ischemic cardiomyopathy (25.5 +/- 2.9 fmol/min/mg, n = 9) and was 48% lower (p less than 0.001) in hearts from patients with idiopathic cardiomyopathy (18.5 +/- 1.9 fmol/min/mg, n = 15). (ABSTRACT TRUNCATED AT 250 WORDS)