title: Differential systemic and pulmonary hemodynamic effects of L-arginine in patients with coronary artery disease or primary pulmonary hypertension.
abstract: The endothelial EDRF/NO-mediated relaxing mechanism is impaired in atherosclerotic and in hypertensive arteries. Recently, it was suggested that primary pulmonary hypertension might be another disease in which the endothelial EDRF/NO pathway is disturbed. We tested the hypothesis that intravenous administration of L-arginine (L-ARG), the physiological precursor of EDRF/NO, stimulates the production of NO, subsequently increasing plasma cGMP levels and reducing systemic and/or pulmonary blood pressure, in patients with coronary artery disease (CAD, n = 16) or with primary pulmonary hypertension (PPH, n = 5). L-ARG (30 g, 150 ml, 15 min) or placebo (150 ml NaCl) was infused in CAD patients, and L-ARG was infused in PPH patients during cardiac catheterization. Mean aortic (Pao) and pulmonary (PAPmean) arterial pressures were continuously monitored. Cardiac output (CO, by thermodilution), total peripheral resistance (TPR), and pulmonary vascular resistance (PVR) were measured before and during the infusions. In CAD patients Pao decreased from 87.2 +/- 4.9 to 81.8 +/- 5.1 mmHg during L-ARG (p < 0.05), whereas PAPmean and PVR were unchanged. TPR decreased from 1008.9 +/- 87.9 to 845.0 +/- 81.7 dyne x sec x cm-5 during L-ARG administration (p < 0.01). CO significantly increased during L-ARG (from 7.3 +/- 2.8 to 8.1 +/- 0.9 l/min, p < 0.05). Placebo did not significantly influence any of the hemodynamic parameters. Plasma cGMP (determined by RIA) slightly increased by 12.2 +/- 9.6% during L-ARG, but slightly decreased during placebo (-12.3 +/- 9.2%) (p < 0.05 for L-ARG vs. placebo). In PPH patients, L-ARG induced no significant change in Pao, TPR, and CO, PAPmean was 59.4 +/- 8.5 mmHg at the beginning of the study and was not significantly reduced by L-ARG nor was PVR (basal: 1042.4 +/- 211.4 dyne x sec x cm-5) changed by L-ARG. Plasma cGMP was not significantly affected by L-ARG in these patients. We conclude that L-ARG stimulates NO production and induces vasorelaxation in CAD patients but not in patients with primary pulmonary hypertension.
authors.affiliation: Institute of Clinical Pharmacology, Medical School, Hannover, Germany.
authors.forename: R H
authors.initials: RH
authors.lastname: Böger
authors.forename: A
authors.initials: A
authors.lastname: Mügge
authors.forename: S M
authors.initials: SM
authors.lastname: Bode-Böger
authors.forename: D
authors.initials: D
authors.lastname: Heinzel
authors.forename: M M
authors.initials: MM
authors.lastname: Höper
authors.forename: J C
authors.initials: JC
authors.lastname: Frölich
mesh_terms: D000328:Adult; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015398:Signal Transduction / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D001120:Arginine; D006152:Cyclic GMP