Importance of angiotensin-converting enzyme in pulmonary hypertension.
Angiotensin II causes pulmonary vasoconstriction in man and in animals, and angiotensin-converting enzyme (ACE) inhibitors have prevented the development of chronic pulmonary hypertension in animals models. Angiotensin II may contribute to lung vascular remodeling in pulmonary hypertensive disease, since cilazapril, an inhibitor of ACE, reduces pulmonary vascular medical thickening in chronically hypoxic rats with established pulmonary hypertension. Furthermore, the ACE DD genotype, which has been associated with increased circulating and tissue ACE activity, has been associated with left ventricular hypertrophy in human hypertensive disorders. The ACE DD genotype may also 'permit' a greater hypertrophic adaptation of the pressure-over-loaded right ventricle. In fact, we have shown that pulmonary hypertension patients with maintained cardiac output and less right-heart failure fall into the group with the DD genotype and that patients with a low cardiac output and more severe right-heart failure fall into the group with the non-DD genotype, supporting the hypothesis. We assessed cardiopulmonary hemodynamics in patients with primary (unexplained) pulmonary hypertension and segregated the patients based on their ACE genotype. For similar mean pulmonary artery pressures in the DD and non-DD groups, the cardiac output was substantially lower in the patients with the non-DD genotype, whereas the values for mean right atrial pressure and pulmonary vascular resistance were double when compared with the DD group. Our data show that the ACE DD genotype is prevalent in patients with severe pulmonary hypertension and is a marker of maintained right ventricular function.
Abraham
W T
WT
University of Colorado Health Sciences Center, Pulmonary Hypertension Center, Denver, USA.
Raynolds
M V
MV
Gottschall
B
B
Badesch
D B
DB
Wynne
K M
KM
Groves
B M
BM
Lowes
B D
BD
Bristow
M R
MR
Perryman
M B
MB
Voelkel
N F
NF
D000818:Animals; D017315:Cilazapril / Q000627:therapeutic use; D004195:Disease Models, Animal; D004587:Electrophoresis, Agar Gel; D005838:Genotype; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects*; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy / Q000503:physiopathology*
D017315:Cilazapril; D007703:Peptidyl-Dipeptidase A