Nitric oxide and cGMP do not affect fluid flux in isolated rat lungs.
We sought to examine the influence of nitric oxide (NO) and the second messengers guanosine 3',5'-cyclic monophosphate (cGMP) and intracellular Ca2+ on fluid flux in lungs isolated from male Sprague-Dawley rats and perfused with saline (containing 4% albumin) or with whole blood. Lungs were allowed to equilibrate for a period of 30 min without treatment (control group) or with one of the following agents: the exogenous NO donor spermine NONOate, the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NNA), 8-BrcGMP, the Ca2- ionophore ionomycin, or the endothelial injurious agent protamine. After equilibration, perfusate reservoir height was increased to five incremental settings to increase pulmonary venous pressure and enhance fluid flux. Perfusate reservoir weight was monitored continuously as an index of fluid flux. The lung wet-to-dry weight ratio was determined on completion of the experiments. Increasing reservoir height was associated with an increase in pulmonary arterial, pulmonary capillary, and pulmonary venous pressures and an increase in fluid flux. However, treatment with exogenous NO or inhibition of endogenous NO was without effect on fluid flux in saline lungs at two different flow rates or in whole blood-perfused lungs. Similarly, treatment with cGMP and ionomycin did not alter fluid flux. Protamine pretreatment resulted in a significant increase in fluid flux at the highest reservoir setting, although exogenous NO and L-NNA pretreatments were without further effect on the protamine-treated lungs. Thus a role for NO and the second messengers cGMP and Ca2+ in modulating fluid flux could not be demonstrated in the isolated rat lung.
Eichinger
M R
MR
Department of Physiology, University of New Mexico School of Medicine, Albuquerque 87131. USA.
Walker
B R
BR
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001826:Body Fluids / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006494:Heparin Antagonists / Q000633:toxicity; D066298:In Vitro Techniques; D015759:Ionomycin; D008168:Lung / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D009589:Nitrogen Oxides; D009929:Organ Size / Q000502:physiology; D011479:Protamines / Q000633:toxicity; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006494:Heparin Antagonists; D009589:Nitrogen Oxides; D011479:Protamines; C091861:spermine nitric oxide complex; D019335:Nitroarginine; D013096:Spermine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D015759:Ionomycin; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D002118:Calcium