Effect of NO synthase inhibition on cardiovascular and pulmonary dysfunction in a porcine short-term model of endotoxic shock.
In a porcine model of endotoxic shock, we evaluated the circulatory and respiratory effects of NO synthase (NOS) blockade. Twenty anaesthetised pigs were divided into three groups and studied for 240 min after induction of endotoxic shock with lipopolysaccharides of Escherichia coli (LPS). After 180 min of endotoxic shock, one group (n = 6) received aminoguanidine, another group (n = 6) received N(G)-nitro-L -arginine methyl ester (L -NAME) and a third group (n = 8) received only LPS. A sham group (n = 3) was also studied. LPS decreased systemic arterial pressure and cardiac output (CO) and increased mean pulmonary arterial pressure (MPAP), pulmonary vascular resistance (PVR) and heart rate. Significant changes were also observed in compliance (-18.4%) and resistance (+33.6%) of the respiratory system. Aminoguanidine did not modify LPS-dependent effects, while, after L -NAME, a significant increase in MPAP, PVR and SVR and a decrease in CO were observed. In conclusion, aminoguanidine does not play a significant cardiocirculatory and pulmonary role in the short-term dysfunction of endotoxic shock, while L -NAME has a detrimental effect on haemodynamics, suggesting a protective role of constitutive NO production at vascular level during the early stages of endotoxaemia.
Albertini
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Dipartimento di Patologia animale, Igiene e Sanità pubblica veterinaria, sez. di Biochimica e Fisiologia, Università degli studi di Milan, Milan, Italy. mariangela.albertini@unimi.it
Lafortuna
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Clement
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Mazzola
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Radice
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Hussain
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D002496:Central Venous Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D012772:Shock, Septic / Q000139:chemically induced / Q000503:physiopathology*; D013552:Swine; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester