Background Pancreatic digestive enzymes present in meconium might be responsible for meconium-induced lung injury. The local Renin Angiotensin System plays an important role in lung injury and inflammation. Particularly, angiotensin converting enzyme-2 (ACE-2) has been identified as a protective lung enzyme against the insult. ACE-2 converts pro-apoptotic Angiotensin II to anti-apoptotic Angiotensin 1-7. However, the effect of meconium on ACE-2 has never been studied before. Objective To study the effect of meconium on ACE-2, and whether inhibition of proteolytic enzymes present in the meconium reverses its effects on ACE-2. Methods Alveolar epithelial A549 cells were exposed to F-12 medium, 2.5% meconium, meconium + a protease inhibitor cocktail (PIc) and PIc alone for 16 h. At the end of incubation, apoptosis was measured with a nuclear fragmentation assay and cell lysates were collected for ACE-2 immunoblotting and enzyme activity. Results Meconium caused a fourfold increase in apoptotic nuclei (p < 0.001). The pro-apoptotic effect of meconium can be reversed by PIc. Meconium reduced ACE-2 enzyme activity by cleaving ACE-2 into a fragment detected at ~ 37 kDa by immunoblot. PIc prevented the degradation of ACE-2 and restored 50% of ACE-2 activity (p < 0.05). Conclusion These data suggest that meconium causes degradation of lung protective ACE-2 by proteolytic enzymes present in meconium, since the effects of meconium can be reversed by PIc.
It would seem that if the liver is the only source of the potassium mobilized in response to the stimulation of epinephrine3 it probably continues to release it during the entire time when the epinephrine level of the blood is elevated. However, the liver, as well as the other tissues, very rapidly begins removing potassium from the blood and at such a rate that the blood potassium level is depressed appreciably below the resting normal. The mechanism by which this is accomplished is not clear and whether it depends upon metabolic or purely vascular factors cannot be said at this time.Summary. During infusion of 1 :75,00 epinephrine for as long as 45 minutes at the rate of 1 ml per minute the potassium content of the blood entering the liver, although actually below the resting concentration still exceeds that of blood leaving the liver. This strongly suggests that the cell source from which potassium is mobilized by epinephrine takes part, at least, in removing the excess from the circulation.
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