Abstract
Acute, diffuse lung injury, the principal lesion in ARDS, is often refractory to treatment. Recently, pretreatment with several pulmonary vasodilators that increase AMP 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 10ml/min with Krebs-4% albumin solution, and ventilated at constant tidal volume(6.5ml/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 2ml/kg. Four rats received 2ml/kg of physiological saline intratracheally as control. In 6 other animals, VIP was infused into the pulmonary artery at 1μg/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 he 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<0.01). PPA initially increased by only 16% and returned to baseline within 15 minutes (p<0.01). Moreover, the lung weight gain was smaller by 52% (p<0.01). VIP post-treatment (one minute or three minutes after the acid-induced lung injury) protected less degree in rise of PAW or PPA and showed no inhibitory effect on the lung weight gain. Atrial natriuretic peptide (ANP), a neuropeptide that has been revealed to possess potent vasodilator action through cGMP-producing activity, was also investigated. Though ANP protected against increase in PAW and PPA caused by acid-induced lung injury, it did not modulate increase in W/D.
We conclude that VIP protects against acid-induced lung injury, including pulmonary hypertension, increased airway pressure, and pulmonary edema. This protective effect of VIP may be related to the increase in cAMP levels in lungs.
