Nitric oxide protects against contrast media-increased pulmonary vascular permeability in rats.
OBJECTIVE
Nitric oxide (NO) regulation of endothelial function is involved in the development of acute lung injury. The role of NO in contrast media-induced increases in pulmonary vascular permeability was investigated in a rat model.


METHODS
Nonionic (iohexol) and ionic (ioxaglate) contrast media were intravenously injected at 1.5 mL/min in rats. Pulmonary vascular permeability was evaluated by measuring the amount of Evans blue dye uptake as a quantitative marker of albumin extravasation in lung tissue.


RESULTS
Intravenous injections of contrast media at doses of 4 and 6 g I/kg induced a dose-dependent increase in pulmonary vascular permeability. L-Arginine (an NO synthase substrate) and N(G)-nitro-L-arginine (L-NNA) (an NO synthase inhibitor) prevented and aggravated, respectively, the increase in pulmonary vascular permeability induced by the contrast medium. An aggravating action of L-NNA was confirmed by morphological and histological observations, this action being blocked by L-arginine (300 mg/kg) but not by D-arginine. Isosorbide dinitrate (1-20 mg/kg), an NO donor, had a dose-dependent protective effect on ioxaglate-increased vascular permeability.


CONCLUSIONS
Our experimental findings suggest that contrast media at high doses produce pulmonary edema by inhibiting endothelial NO production, and nitrovasodilators protect against this adverse effect in rats.
Sendo
T
T
Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kataoka
Y
Y
Takeda
Y
Y
Furuta
W
W
Oishi
R
R
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007275:Injections, Intravenous; D007472:Iohexol / Q000008:administration & dosage / Q000009:adverse effects; D007485:Ioxaglic Acid / Q000008:administration & dosage / Q000009:adverse effects; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D003287:Contrast Media; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D007472:Iohexol; D001120:Arginine; D019001:Nitric Oxide Synthase; D007548:Isosorbide Dinitrate; D007485:Ioxaglic Acid