endothelin-1 and Asphyxia

Xinmailong, a compound extracted from Periplaneta americana, is used for the treatment of cardiovascular diseases. This study investigated the effects of Xinmailong on myocardial hypoxia-inducible factor-1alpha (HIF-1alpha) and plasma endothelin-1(ET-1) levels in neonatal rats with asphyxia and explored the protection mechanism of Xinmailong in hypoxia-ischemic myocardial injury.. Seven-day-old Sprague-Dawley rats were randomly divided into three groups (n=30 each): sham-operated, asphyxia, Xinmailong-treated asphyxia. Each group was randomly subdivided into three groups according to the observed time points: 6 hrs, 24 hrs and 72 hrs. Xinmailong (5 mg/kg) was intraperitoneally injected to the rats in the Xinmailong-treated group five minutes before asphyxia. Myocardial HIF-1alpha expression, and plasma ET-1 and creatine kinase (CK) levels were measured. The histopathologic changes of the myocardium were observed by hematoxylin-eosin staining.. Four rats died in the asphyxia group while only one died in the Xinmailong-treated group during the experiment. The plasma ET-1 and CK levels as well as myocardial HIF-1alpha expression increased at 6 hrs, reached a peak at 24 hrs, and declined at 72 hrs after asphyxia in the asphyxia group, being higher than that in the sham-operated group (P<0.01). Myocardial ischemia was observed in the three time points, and cell necrosis occurred at 24 hrs after asphyxia in the asphyxia group. Myocardial HIF-1alpha expression was positively correlated with plasma ET-1 levels (r=0.876, P<0.01). In the Xinmailong-treated group, plasma levels of CK and ET-1 as well as myocardial HIF-1alpha expression were significantly lower than those in the asphyxia group (P<0.01). Myocardial ischemia was alleviated and no cell necrosis was found in the Xinmailong-treated group.. Asphyxia leads to increase in myocardial HIF-1alpha expression and plasma levels of ET-1 and CK. Xinmailong can reduce the myocardial expression of HIF-1alpha and decrease plasma ET-1 levels, thus alleviating hypoxia-ischemic myocardial injury.

Topics: Animals; Animals, Newborn; Asphyxia; Creatine Kinase; Endothelin-1; Female; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Male; Myocardial Ischemia; Myocardium; Periplaneta; Rats; Rats, Sprague-Dawley

The aim of this study was to evaluate changes in intestinal microcirculation during necrotizing enterocolitis (NEC) and to examine the effect of endothelin (ET)-1 on the intestinal microcirculation. Prematurely born rats were either hand-fed formula (NEC) or dam fed (DF) and were exposed to asphyxia and cold stress twice daily to induce disease. At 0, 2, 3, and 4 d after the birth, the microcirculation in the ileum was examined using in vivo microscopic methods. The nutritive microvascular perfusion in the NEC group was progressively compromised from d 3 to d 4 (35% and 50% decrease, respectively) when compared with DF rats. Concomitantly, intestinal blood flow assessed by laser Doppler flowmetry was significantly reduced at d 2, 3, and 4 (by 31%, 36%, and 73%, respectively). Levels of ET-1 mRNA in the ileum were increased 3.7-fold. Microvascular responses to topically applied ET-1 were significantly increased in the NEC group, which was associated with decreased expression of ETB receptor. These results suggest that microcirculatory dysfunction in the distal ileum of neonatal rats with NEC contributes to disease progression and that enhanced microvascular responsiveness to ET-1 may participate in these microcirculatory disturbances.

Topics: Animals; Animals, Newborn; Asphyxia; Disease Models, Animal; Disease Progression; Endothelin-1; Enterocolitis, Necrotizing; Ileum; Laser-Doppler Flowmetry; Microcirculation; Rats; Rats, Sprague-Dawley; Receptors, Endothelin