NG-methyl-L-arginine restores arterial pressure in hemorrhaged rats.
NG-methyl-L-arginine (NMA) has been shown to inhibit nitric oxide production in vascular endothelium in vitro, and to cause vascular constriction and pressor responses in vivo. This study evaluated the ability of NMA to restore arterial pressure in hemorrhaged rats in order to determine the role of nitric oxide in modulating vascular tone following hemorrhage. Rats were anesthetized with pentobarbital, and hemorrhaged (0.5 ml/min/100 g body weight for 2 min) to a pressure of 41 +/- 4 mm Hg (control 111 +/- 5 mm Hg). Five minutes after ending the hemorrhage, administration of NMA (30 mg/kg, i.v.) caused rapid and complete restoration of arterial pressure, due primarily to increased systemic vascular resistance. Administration of L-arginine before NMA greatly attenuated the pressor response to NMA. NMA caused similar pressor responses in nonhemorrhaged rats, which were also partially blocked by L-arginine. Cardiac output was transiently increased by NMA in hemorrhaged, but not in nonhemorrhaged, animals. These results support the hypothesis that endothelial nitric oxide production has a significant modulatory effect on vascular tone during hemorrhage, and that inhibition of nitric oxide production permits greater expression of vasoconstrictor influences.
Klabunde
R E
RE
Department of Pharmacology, Abbott Laboratories, Abbott Park, IL 60064.
Slayton
K J
KJ
Ritger
R C
RC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D007022:Hypotension / Q000188:drug therapy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D001120:Arginine