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 us ing a nonspecific inhibitor of the constitutive and inducible nitric oxide synthase (NOS), N-methyl-L-arginine (L-NMA), and a specific inhibitor of th e inducible NOS, aminoguanidine, in conscious pigs. Animals were divided in to two groups. After hemodynamics were stabilized, animals in group 1 (n = 5) received an infusion of L-NMA at 300 mug/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 pr essure, 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, hep atic, and renal vascular resistance increased significantly by 95%, 110%, a nd 20%, respectively, at 60 min after L-NMA infusion. Finally, heart rate, cardiac output, dP/dt, and portal and mesenteric blood flows remained uncha nged after L-NMA infusion. In contrast, aminoguanidine infused at 1 mg/kg p er min over 60 min did not change systemic arterial blood pressure or regio nal blood flow in conscious pigs. Furthermore, aminoguanidine had no effect on acetylcholine vasodilator effects. In conclusion, the lack of presser e ffects and of agonist-stimulated NO production induced by aminoguanidine su ggests that aminoguanidine is a weak inhibitor of the constitutive NOS. Com pared with L-NMA, the selectivity of aminoguanidine may decrease possible s ide effects that could occur as a result of inhibition of constitutive NOS.