Angiotensin II-forming pathways in normal and failing human hearts.
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)
Urata
H
H
Department of Heart and Hypertension Research, Cleveland Clinic Foundation, OH 44195-5071.
Healy
B
B
Stewart
R W
RW
Bumpus
F M
FM
Husain
A
A
D000293:Adolescent; D000328:Adult; D000803:Angiotensin I / Q000097:blood / Q000378:metabolism; D000804:Angiotensin II / Q000097:blood / Q000502:physiology*; D002216:Captopril / Q000494:pharmacology; D002303:Cardiac Output, Low / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006352:Heart Ventricles; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012016:Reference Values; D013025:Glycine max / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000494:pharmacology
D014361:Trypsin Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A