[Vasoactive intestinal peptide (VIP) protects against acid-induced acute lung injury in isolated perfused rat lungs].
Acute, diffuse lung injury, the principal lesion in ARDS, is often refractory to treatment. Recently, pretreatment with several pulmonary vasodilators that increase cAMP levels: isoproterenol, terbutaline, theophylline, and prostacyclin, was found to reduce the severity of lung injury in animal models. We have investigated the possible modulation of HCl-induced pulmonary edema in rats by VIP, a lung neuropeptide with potent vasodilator and cAMP-producing properties. The lungs of rats were perfused in situ at 10 ml/min with Krebs-4% albumin solution, and ventilated at constant tidal volume (6.5 ml/kg). Peak airway pressure (PAW), mean pulmonary arterial pressure (PPA) were measured throughout the experiment, and wet to dry lung weight ratio (W/D), afterwards. All animals were observed for one hour. In 6 rats receiving HCl only, 0.2 N-HCl was instilled intratracheally at 2 ml/kg. Four rats received 2 ml/kg of physiological saline intratracheally as control. In 6 other animals, VIP was infused into the pulmonary artery at 1 micrograms/kg/min, beginning 10 minutes before HCl and for the rest of the experiment. Another 6 rats were pretreated with atrial natriuretic peptide (ANP, atriopeptin II) just like the VIP group. Lungs of saline control animals showed little or no chage in PAW or PPA. With HCl alone, PAW increased immediately and continued to rise for the rest of the hour, reaching 500% of basal value at 30 minutes. PPA increased by 68% and W/D by 74% compared to saline-instilled lungs. In the VIP + HCl group, all abnormalities were significantly reduced relative to the HCl group. The rise in PAW was attenuated by 79% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Iwanaga
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Kitamura
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Hirose
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Said
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D000208:Acute Disease; D000818:Animals; D002057:Burns, Chemical / Q000150:complications*; D006851:Hydrochloric Acid; D066298:In Vitro Techniques; D055370:Lung Injury; D008297:Male; D011654:Pulmonary Edema / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D014660:Vasoactive Intestinal Peptide / Q000627:therapeutic use*
D014660:Vasoactive Intestinal Peptide; D006851:Hydrochloric Acid