NG-nitro L-arginine methyl ester: systemic and pulmonary haemodynamics, tissue blood flow and arteriovenous shunting in the pig.
The effects of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the endothelial nitric oxide (NO) biosynthesis, on systemic and pulmonary haemodynamics, and tissue as well as arteriovenous anastomotic blood flows were investigated in the anaesthetized pig, using simultaneous injections of radioactive microspheres of two different sizes (diameter: 15 and 50 microns). L-NAME (1, 3 and 10 mg.kg-1) reduced systemic and pulmonary artery conductance and cardiac output, but heart rate and mean arterial blood pressure remained unchanged. L-arginine reversed the systemic and pulmonary haemodynamic changes induced by L-NAME. As detected with 15 microns microspheres, L-NAME (1 and 3 mg.kg-1) decreased tissue blood flow to and vascular conductance in the eyes, lungs, atria, kidneys, adrenals and liver. Furthermore, the difference between blood flows simultaneously measured with 15 and 50 microns microspheres, which can be equated to blood flow through arteriovenous anastomoses with a diameter between about 28 and 90 microns, was reduced by L-NAME (3 mg.kg-1) in the skin of head and gluteal regions and, as indicated by the microsphere content of the lungs, in the total systemic circulation. These results suggest that in the anaesthetized pig (i) NO is involved in the regulation of both systemic and pulmonary vascular conductance, (ii) the decrease in systemic vascular conductance is in part due to constriction of systemic arteriovenous anastomoses, and (iii) the decrease in pulmonary vascular conductance, leading to reduction of cardiac output, seems to negate the expected rise in arterial blood pressure observed, for example, in rats and rabbits following inhibition of NO-synthesis.
van Gelderen
E M
EM
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands.
Den Boer
M O
MO
Saxena
P R
PR
D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001163:Arteriovenous Anastomosis / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008863:Microspheres; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester