HEMODYNAMIC AND HORMONAL EFFECTS OF N-NITRO-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE BIOSYNTHESIS, IN SHEEP

1. The haemodynamic and hormonal responses to N-nitro-L-arginine (NOLA), a potent inhibitor of nitric oxide biosynthesis in endothelial cells, were investigated in conscious sheep. 2. Mean arterial blood pressure (MAP), heart rate (HR) and cardiac output by thermodilution (CO) were measured in four oophrectomized ewes. Two other ewes were surgically implanted with aortic electromagnetic flow probes and an indwelling carotid arterial line for monitoring CO and MAP over 40 h. 3. After a control period, NOLA (10 mg/kg) was injected intravenously and MAP, HR and CO monitored and blood samples taken at intervals over the following 24 h. 4. NOLA increased blood pressure within minutes, from 76 +/- 4 to a maximum of 99 +/- 4 mmHg (P < 0.001) at 6 h after injection. It remained elevated 24 h after injection. CO and HR fell but these falls were not sustained longer than 6 h. Calculated total peripheral resistance increased to a maximum of 2 h, but had returned to control levels 24 h after injection. There were no significant changes in plasma concentrations of renin, atrial natriuretic factor, vasopressin, noradrenaline or endothelin during the first hour. 5. NOLA may be a useful tool in understanding the role of the endothelium and nitric oxide in the control of blood pressure.