THE CARDIOVASCULAR EFFECTS OF THE ADMINISTRATION OF L-NAME DURING THEEARLY POSTHEMORRHAGIC PERIOD

1. The effects of the various doses of N-G-nitro-L-arginine methyl est er (L-NAME, 10 and 30 mg/kg) on some cardiovascular and biochemical pa rameters during the early posthemorrhagic period were studied in anest hetized rabbits subjected to hemorrhagic hypovolemia. 2. Hemorrhagic s hock was produced by intermittent bleeding of 40% of the estimated blo od volume for 15 min. Blood samples were taken before and after bleedi ng (0, 15 and 60 min). Simultaneously, the mean arterial pressure (MAP ) and the heart rate (HR) were measured. Hemorrhaged rabbits were trea ted by L-NAME(10) or t-NAME(30) (10 or 30 mg/kg, IV bolus injection, r espectively) or the corresponding volumes of saline (0.6 ml, IV bolus) immediately after the end of bleeding. 3. The observed cardiovascular parameters (MAP, HR) were significantly reduced after the end of blee ding in all rabbits. 4. The rise of the MAP was significantly more pro nounced 30 min after the injection of L-NAME(30) in comparison with th e corresponding values in the saline (S) group. In contrast, L-NAME(10 ) produced only a small, insignificant increase in the MAP in hemorrha ged rabbits. 5. The L-NAME(30)-induced rise of the MAP was accompanied by a severe bradycardia, hyperkalemia and an aggravated metabolic aci dosis, more severe than the corresponding disturbance of the acid-base status in the S group. The changes in the acid-base parameters were o bserved both in arterial (pH, excess base) and in venous blood (pH) of hemorrhaged rabbits. 6. In conclusion, the IV bolus injection of L-NA ME(30) (immediately after the end of bleeding) produced a significant increase in the MAP during the first hour after the injury, but the pr esumable inhibition of the endothelial constitutive nitric oxide synth ase during the early posthemorrhagic period resulted in severe cardiov ascular and metabolic disturbances. (C) 1998 Elsevier Science Inc.