The Cardiovascular Effects of the Administration of l-NAME during the Early Posthemorrhagic Period

• Published in: General pharmacology Vol. 30; no. 5; pp. 763 - 769
• Main Authors: Todorović, Zoran, Prostran, Milica S̆, Varagić, Vladislav, Z̆unić, Gordana, Savić, Jovan, Vujnov, Stojanka
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.1998; Elsevier
• Subjects: Animals; Biological and medical sciences; Blood Pressure - drug effects; Blood Proteins - drug effects; cardiovascular parameters; Cardiovascular system; Electrolytes - metabolism; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - pharmacology; Heart - drug effects; Heart - physiology; Heart Rate - drug effects; hemorrhagic shock; Hydrogen-Ion Concentration - drug effects; l-NAME; Medical sciences; Miscellaneous; NG-Nitroarginine Methyl Ester - administration & dosage; NG-Nitroarginine Methyl Ester - adverse effects; NG-Nitroarginine Methyl Ester - pharmacology; Pharmacology. Drug treatments; Rabbits; Shock, Hemorrhagic - blood; Shock, Hemorrhagic - drug therapy; Shock, Hemorrhagic - physiopathology; hemorrhagic shock; l-NAME; cardiovascular parameters; Shock; Cardiac performance; Intravenous administration; Rabbit; Cardiovascular disease; Lagomorpha; Hemorrhage; Dose activity relation; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Hemodynamics
• ISSN: 0306-3623; 1879-0011
• DOI: 10.1016/S0306-3623(97)00333-9

1. The effects of the various doses of N G-nitro- L-arginine methyl ester ( L-NAME, 10 and 30 mg/kg) on some cardiovascular and biochemical parameters during the early posthemorrhagic period were studied in anesthetized rabbits subjected to hemorrhagic hypovolemia. 2. Hemorrhagic shock was produced by intermittent bleeding of 40% of the estimated blood volume for 15 min. Blood samples were taken before and after bleeding (0, 15 and 60 min). Simultaneously, the mean arterial pressure (MAP) and the heart rate (HR) were measured. Hemorrhaged rabbits were treated by L-NAME 10 or L-NAME 30 (10 or 30 mg/kg, IV bolus injection, respectively) 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 bleeding in all rabbits. 4. The rise of the MAP was significantly more pronounced 30 min after the injection of L-NAME 30 in comparison with the corresponding values in the saline (S) group. In contrast, L-NAME 10 produced only a small, insignificant increase in the MAP in hemorrhaged rabbits. 5. The L-NAME 30-induced rise of the MAP was accompanied by a severe bradycardia, hyperkalemia and an aggravated metabolic acidosis, more severe than the corresponding disturbance of the acid-base status in the S group. The changes in the acid-base parameters were observed both in arterial (pH, excess base) and in venous blood (pH) of hemorrhaged rabbits. 6. In conclusion, the IV bolus injection of L-NAME 30 (immediately after the end of bleeding) produced a significant increase in the MAP during the first hour after the injury, but the presumable inhibition of the endothelial constitutive nitric oxide synthase during the early posthemorrhagic period resulted in severe cardiovascular and metabolic disturbances.