Nitric oxide and endothelin relationship in intestinal ischemia/reperfusion injury (II)

Endothelins (ETs) are potent vasoconstrictors derived from vascular endothe lium. They have primary roles in many pathophysiologic states including isc hemia/reperfusion (I/R) injury. The relationships between nitric oxide (NO) and ETs are still under investigation. In this study on rats we want to fo cus on the interaction of NO and ET especially in I/R injury. For this purp ose ET-1 and PD-156252, a nonselective ET receptor blocker, were given in a mesenteric I/R model and reactive oxygen species were detected directly us ing chemiluminescence of the ileal tissue. ET administrations to sham and I /R groups caused significant increases in NO concentrations whereas, in ter ms of peroxynitrite, which is a highly reactive group of free radicals, its increasing effects were seen only in I/R groups. This suggests that in I/R where superoxide levels increase together with NO, the conversion to perox ynitrite is likely and this effect is augmented with ET administration. On the other hand PD administration decreases superoxide and thereby peroxynit rite levels and this study shows that the effect of PD-156252 is establishe d through this mode of action. These data suggest therapeutic approaches th at may be beneficial in the treatment of I/R injury. (C) 2001 Harcourt Publ ishers Ltd.