GADOLINIUM CHLORIDE INHIBITION OF PULMONARY NITRIC-OXIDE PRODUCTION AND EFFECTS ON PULMONARY CIRCULATION IN THE RABBIT

Nitric oxide is an important regulator of pulmonary vascular resistanc e. Pulmonary nitric oxide formation is detectable in exhaled air and t he synthesis is partly stretch-dependent. Gadolinium chloride (GdCl3) reduces pulmonary nitric oxide formation, possibly by interference wit h stretch-activated cellular calcium influx, but the effect on pulmona ry circulation is not known. We therefore measured exhaled nitric oxid e and pulmonary vascular resistance in anaesthetised rabbits, and comp ared the effects of GdCl3 with those of an nitric oxide-synthase inhib itor (L-N-omega-nitro-arginine methyl ester, L-NAME). Both GdCl3 and L -NAME reduced nitric oxide in exhaled air and increased pulmonary vasc ular resistance. However, the increase in pulmonary vascular resistanc e was more pronounced with GdCl3 than with L-NAME. A 50% reduction of exhaled nitric oxide caused by either GdCl3 or L-NAME was accompanied by a 90% or 17% increase in pulmonary vascular resistance respectively . Inhaled nitric oxide (40 ppm) reduced pulmonary vascular resistance after L-NAME, but not after GdCl3 infusion. Infusion of glyceryltrinit rate reduced pulmonary vascular resistance after GdCl3 infusion. GdCl3 caused hypoxaemia, probably due to vasoconstriction since lung weight was unaltered. Thus GdCl3 can induce a marked increase in pulmonary v ascular resistance, which partly may be caused by inhibition of pulmon ary nitric oxide formation. Intact stretch-activated calcium channels may be important for maintenance of normal pulmonary vascular function .