Comparison of cardiac and regional hemodynamic responses to N-methyl-L-arginine and aminoguanidine infusions in conscious pigs.
The aim of this study was to elucidate cardiac and regional hemodynamics using a nonspecific inhibitor of the constitutive and inducible nitric oxide synthase (NOS), N-methyl-L-arginine (L-NMA), and a specific inhibitor of the inducible NOS, aminoguanidine, in conscious pigs. Animals were divided into two groups. After hemodynamics were stabilized, animals in group 1 (n = 5) received an infusion of L-NMA at 300 microg/kg per min, i.v., over 60 min, and group 2 (n = 5) received an infusion of aminoguanidine, infused at 1 mg/kg per min over 60 min. Hemodynamic parameters including arterial blood pressure, heart rate, cardiac output, dP/dt, and carotid, coronary, hepatic, portal, mesenteric, and renal blood flows were continuously recorded before and 5, 15, 30, 45, 60, and 120 min after L-NMA infusion or aminoguanidine infusion, or both. The L-NMA vasopressor response (20%) was associated with a significant increase in systemic vascular resistance (45%). Carotid, hepatic, and renal vascular resistance increased significantly by 95%, 110%, and 20%, respectively, at 60 min after L-NMA infusion. Finally, heart rate, cardiac output, dP/dt, and portal and mesenteric blood flows remained unchanged after L-NMA infusion. In contrast, aminoguanidine infused at 1 mg/kg per min over 60 min did not change systemic arterial blood pressure or regional blood flow in conscious pigs. Furthermore, aminoguanidine had no effect on acetylcholine vasodilator effects. In conclusion, the lack of pressor effects and of agonist-stimulated NO production induced by aminoguanidine suggests that aminoguanidine is a weak inhibitor of the constitutive NOS. Compared with L-NMA, the selectivity of aminoguanidine may decrease possible side effects that could occur as a result of inhibition of constitutive NOS.
Doursout
M F
MF
Department of Anesthesiology, The University of Texas-Houston Health Science Center, USA.
Hartley
C J
CJ
Chelly
J E
JE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D006146:Guanidines; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; C004479:pimagedine