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 intracellu lar 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 trea tment (control group) or with one of the following agents: the exogeno us NO donor spermine NONOate, the nitric oxide synthase inhibitor N-om ega-nitro-L-arginine (L-NNA), 8-BrcGMP, the Ca2+ ionophore ionomycin, or the endothelial injurious agent protamine. After equilibration, per fusate reservoir height was increased to five incremental settings to increase pulmonary venous pressure and enhance fluid flux. Perfusate r eservoir weight was monitored continuously as an index of fluid flux. The lung wet-to-dry weight ratio was determined on completion of the e xperiments. Increasing reservoir height was associated with an increas e in pulmonary arterial, pulmonary capillary, and pulmonary venous pre ssures and an increase in fluid flux. However, treatment with exogenou s NO or inhibition of endogenous NO was without effect on fluid flux i n saline lungs at two different flow rates or in whole blood-perfused lungs. Similarly, treatment with cGMP and ionomycin did not alter flui d flux. Protamine pretreatment resulted in a significant increase in f luid flux at the highest reservoir setting, although exogenous NO and L-NNA pretreatments were without further effect on the protamine-treat ed lungs. Thus a role for NO and the second messengers cGMP and Ca2+ i n modulating fluid flux could not be demonstrated in the isolated rat lung.