Effects of losartan + L-arginine on nitric oxide production, endothelial cell function, and hemodynamic variables in patients with heart failure secondary to coronary heart disease.
The purpose of the present study was to evaluate the effects of losartan and the combination of losartan and L-arginine on endothelial function and hemodynamic variables in patients with heart failure (HF). Endothelium-dependent vasodilation is impaired in patients with HF. It was hypothesized that the administration of losartan and the combination of losartan and L-arginine might increase nitric oxide production and have a beneficial additive effect on endothelial function and hemodynamic variables in patients with HF. Nine patients with HF (ejection fraction<35%) were given losartan 50 mg orally on 2 consecutive days. On the second day, 1 hour after losartan 50 mg administration, L-arginine 20 g was given by intravenous infusion. Endothelial function in the form of endothelium-dependent brachial artery flow-mediated vasodilation (FMV) was measured by ultrasound. Hemodynamic variables were estimated using Doppler echocardiography at baseline and at 2 and 4 hours after losartan alone and after combination therapy. Urinary levels of nitrite (NO2) or nitrate (NO3) were measured. Four hours after losartan administration, significant reductions in systemic vascular resistance and estimated end-systolic elastase were observed. On the second day, 1 hour after L-arginine infusion, an additive hemodynamic effect was observed, with significant increases in the cardiac index and stroke volume and significant reductions in systemic vascular resistance and calculated left ventricular end-diastolic pressure. A trend toward improved FMV was observed with losartan alone, but without statistical significance. Combination therapy significantly improved postintervention FMV compared with baseline. The increase in urinary nitric oxide excretion after losartan treatment and combination therapy was significantly correlated with improved hemodynamic variables and improved FMV. In conclusion, losartan induces significant afterload reduction, reduced contractility, and increased nitric oxide urinary excretion. The combination of L-arginine and losartan seems to have superior effects on hemodynamic variables and endothelium-dependent vasodilation compared with losartan alone.
Koifman
Bella
B
Department of Cardiology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Topilski
Ian
I
Megidish
Ricki
R
Zelmanovich
Laslo
L
Chernihovsky
Tamara
T
Bykhovsy
Elda
E
Keren
Gad
G
D000284:Administration, Oral; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D003327:Coronary Disease / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D016896:Treatment Outcome; D018608:Ultrasonography, Doppler; D014664:Vasodilation / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D009569:Nitric Oxide; D001120:Arginine; D019808:Losartan