DYNAMIC STUDY OF NITRIC-OXIDE AND ENDOTHELIN-1 DURING ENDOTOXIN-SHOCKAND EFFECTS OF THEIR ANTAGONISTS ON HEMODYNAMICS

Objective To examine the relationship between the profound hypotension in endotoxic shock and the dynamic changes of nitric oxide (NO) and e ndothelin-l (ET-1), so as to figure out which of the NO or ET-1 was mo re involved in the pathogenesis of endotoxic shock. And to investigate whether an offset of their opposite vasoactive effects would occur du ring endotoxic shock. Methods 24 rabbits were anesthetized and instrum ented for recording hemodynamics. Endotoxin (E. coli 026:B6, 600 mu g/ kg) was bolus injected intravenously and the animals were randomly div ided into four groups. Group I was control without any more interventi on, and Group II, ill, IV received bolus injections of L-NMA (10 mg/kg ), phosphoramidon (2 mg/kg) or dexamethasone (2 mg/kg) respectively at 30 min post-endotoxin. Plasma NO3-, ET-1 and hemodynamics were measur ed at regular intervals. Their relationships were compared and analyse d. Results Plasma ET-1 achieved its peak level at 60 min post-endotoxi n, and then waned. Plasma NO3 started rising at 120 min post-endotoxin , then progressive increase continued till the last measurement at 180 min post-endotoxin. The decrease of blood pressure was significant at about 120 min post-endotoxin and further went down until death. The c hanges of hemodynamics and NO showed a quite close temporal correspond ence between the increase of NO and the decrease of blood pressure. L- NMA and phosphoramidon obviously reduced the plasma levels of NO and E T-1 to below their respective baseline levels, and showed transient ef fect of increase on blood pressure. Soon afterwards, however, the stat us of hemodynamics was aggravated. Dexamethasone just inhibited the ex cessive increase of NO and ET-1 during endotoxic shock without interfe ring their baseline levels and showed most beneficial effects on hemod ynamics. Conclusions Both NO and ET-1 increase during endotoxic shock, but only the increase of NO has a close temporal correspondence with the decrease of blood pressure. It suggests a more important role of N O in pathogenesis of endotoxic shock. The increase of NO and PT-I is d ifferent in time-process, which indicates that an offset of their oppo site vasoactive effects would not occur. Intreference against the incr ease of NO and ET-1 during endotoxic shock is most beneficial when the ir baseline levels are maintained.