Perfusate viscosity and hematocrit determine pulmonary vascular responsiveness to NO synthase inhibitors.
The pulmonary vascular responses to changes in perfusate viscosity were studied in isolated rat lungs treated with the nitric oxide synthase (NOS) inhibitors, N omega-nitro-L-arginine methyl ester (L-NAME) and N omega- monomethyl-L-arginine (L-NMMA). Lungs were isolated according to standard protocols and perfused with varying concentrations of albumin in physiological salt solution (PSS) and with low, intermediate, and normal hematocrits using washed erythrocytes. Pressure-flow curves were generated by increasing pulmonary arterial pressure (PPA) while keeping pulmonary venous pressure (PPV) constant and measuring flow at each pressure interval. Neither perfusate flow nor pulmonary vascular resistance changed after L-NAME or L-NMMA (300 microM) at any pressure interval in lungs perfused with 4 and 10% albumin/PSS. In lungs perfused with 20% albumin/PSS, L-NMMA decreased flow at all PPA tested except 10 cm H2O (P < 0.05). L-NAME decreased flow in lungs perfused with normal (39.2 +/- 2.1%) hematocrits at all PPA tested. Conversely, L-NAME decreased flow in lungs perfused with low and intermediate hematocrits only at the highest pressure intervals. L-Arginine, when given after NOS inhibitors, failed to restore flow to baseline values in any group of lungs. N omega-nitro-D-arginine methyl ester (300 microM) did not change flow at any pressure interval in lungs perfused with normal (43 +/- 1.5%) hematocrit, washed erythrocytes. We conclude that lungs perfused with intermediate and normal hematocrit, washed erythrocytes, as well as with high-viscosity albumin/PSS solutions, show increased pulmonary vascular responses to NOS inhibitors.
Wilson
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PS
Department of Physiology, University of South Alabama College of Medicine, Mobile 36688, USA.
Khimenko
P
P
Moore
T M
TM
Taylor
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AE
D000818:Animals; D004912:Erythrocytes; D006400:Hematocrit; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin; D012965:Sodium Chloride; D014655:Vascular Resistance / Q000187:drug effects; D014783:Viscosity; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D012709:Serum Albumin; D019323:omega-N-Methylarginine; D012965:Sodium Chloride; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester