DIFFERENTIAL SYSTEMIC AND PULMONARY HEMODYNAMIC-EFFECTS OF L-ARGININEIN PATIENTS WITH CORONARY-ARTERY DISEASE OR PRIMARY PULMONARY-HYPERTENSION

The endothelial EDRF/NO-mediated relaxing mechanism is impaired in ath erosclerotic 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 physiologi cal precursor of EDRF/NO, stimulates the production of NO, subsequentl y 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, 15 0 mi, 15 min) or placebo (150 ml NaCl) was infused in CAD patients, an d L-ARG was infused in PPH patients during cardiac catheterization. Me an aortic (P-ao) and pulmonary (PAP(mean)) arterial pressures were con tinuously monitored. Cardiac output (GO, by thermodilution), total per ipheral resistance (TPR), and pulmonary vascular resistance (PVR) were measured before and during the infusions. In CAD patients P-ao decrea sed from 87.2 +/- 4.9 to 81.8 +/- 5.1 mmHg during L-ARG (p < 0.05), wh ereas PAP(mean) 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 influe nce any of the hemodynamic parameters. Plasma cGMP (determined by RIA) slightly increased by 12.2 +/- 9.6% during L-ARG, but slightly decrea sed during placebo (-12.3 +/- 9.2%) (p < 0.05 for L-ARG vs. placebo). In PPH patients, L-ARG induced no significant change in P-ao, TPR, and CO. PAP(mean) 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 sign ificantly affected by L-ARG in these patients. We conclude that L-ARG stimulates NO production and induces vasorelaxation in CAD patients bu t not in patients with primary pulmonary hypertension.