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 resistance. Pulmonary nitric oxide formation is detectable in exhaled air and the synthesis is partly stretch-dependent. Gadolinium chloride (GdCl3) reduces pulmonary nitric oxide formation, possibly by interference with stretch-activated cellular calcium influx, but the effect on pulmonary circulation is not known. We therefore measured exhaled nitric oxide and pulmonary vascular resistance in anaesthetised rabbits, and compared the effects of GdCl3 with those of an nitric oxide-synthase inhibitor (L-N omega-nitro-arginine methyl ester, L-NAME). Both GdCl3 and L-NAME reduced nitric oxide in exhaled air and increased pulmonary vascular resistance. However, the increase in pulmonary vascular resistance 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 glyceryltrinitrate 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 vascular resistance, which partly may be caused by inhibition of pulmonary nitric oxide formation. Intact stretch-activated calcium channels may be important for maintenance of normal pulmonary vascular function.
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Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Bannenberg
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Gustafsson
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D000818:Animals; D001784:Blood Gas Analysis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology*; D006403:Hematologic Tests; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011654:Pulmonary Edema / Q000139:chemically induced; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D005682:Gadolinium; D005996:Nitroglycerin; C038958:gadolinium chloride; D019331:NG-Nitroarginine Methyl Ester