[The effect of NG-nitro-L-arginine administration on the hemodynamics and plasma hormone levels during endotoxin shock in dogs].
Although various mediators such as platelet activating factor, anaphylatoxin and cytokines are considered to be involved in the pathology of endotoxin-induced shock, an endothelium-derived relaxing factor (EDRF), nitric oxide (NO) or its related substance, has recently been shown as a vasodilating factor that is produced from L-arginine. On the other hand, NG-nitro-L-arginine (L-NNA) is shown to inhibit NO production from L-arginine. Thus, in order to examine a possible involvement of NO in the shock, the effect of L-NNA administration was studied on the hemodynamics and plasma hormone levels during endotoxin-induced shock in anesthetized dogs. Twenty-five mongrel dogs were divided into the following 5 groups; (1) In group C, only physiological saline was administered. (2) In group L, a bolus injection of L-NNA (4 mg/kg B.W.) was followed by a continuous infusion of the agent (0.05 mg/kg B.W./min) for 120 min. (3) In group E, lipopolysaccharide (LPS) E. Coli 011:B4 2.625 mg/kg body weight was administered. (4) In group LE, L-NNA administration (bolus and continuous) the same as in group L was started 5 min before the injection of LPS. (5) In group EL, L-NNA administration (bolus and continuous) was started 5 min after the injection of LPS. In Group LE, MAP decreased to -45.9 mmHg 5 min after LPS injection and -33.0 mmHg 120 min from pre-level. The levels of MAP from 15 to 90 min were significantly higher than those in Group E. In Group EL, MAP decreased to -61.4 mmHg 5 min after LPS injection and this low level (-59.5 mmHg) continued for 120 min. A protecting effect of L-NNA against LPS-induced hypotension was clearly observed only when administration of the agent was started before LPS injection. These results indicated that LPS induced shock could be produced by a possible increase of NO production in the vascular endothelial cells. The other finding in the present experiment using anesthetized animals was that L-NNA had a stimulatory action on some endocrine systems such as the renin-aldosterone system and pituitary-adrenal axis, although the exact mechanism of this action of L-NNA on such systems was unclear.
Department of Endocrinology, Internal Medicine, Dokkyo University School of Medicine.
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Takekoshi
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Kasai
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Nakamura
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D012083:Renin / Q000097:blood; D012772:Shock, Septic / Q000503:physiopathology*
D006728:Hormones; D019335:Nitroarginine; D009569:Nitric Oxide; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D001120:Arginine; D012083:Renin; D006854:Hydrocortisone