Reversal by L- and D-enantiomers of NG-nitro-arginine of endotoxin-induced hypotension and vascular hyporesponsiveness.
We examined the effects of D-NNA (NG-nitro-D-arginine) and L-NNA (NG-nitro-L-arginine) on suppression of Escherichia coli lipopolysaccharide (LPS)-induced vascular hyporeactivity in pentobarbital-anesthetized rats. Mean arterial pressure (MAP) and pressor response to norepinephrine (NE) were reduced at 40 min (early phase) and 3.5-4 h (late phase) after i.v. injection of LPS (10 mg/kg). Pretreatment with either D-NNA (16 mg/kg) or L-NNA (8 mg/kg) abolished LPS-induced reduction in MAP and hyporesponsiveness to NE during the early phase but not the late phase of endotoxemia and increased mortality. In contrast, posttreatment with D-NNA and L-NNA at 3 h after the injection of LPS prevented further decreases of MAP and pressor response to NE during the late phase of endotoxemia. The restoration of vascular response by pretreatment with either D-NNA or L-NNA during the early phases or posttreatment with either of these two agents during the late phase of endotoxemia was abolished by i.v. infusion (10 mg/kg/min) of L-arginine (L-Arg), but not D-arginine (D-Arg), suggesting involvement of the L-Arg/ nitric oxide pathway.
Cheng
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X
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Wang
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YX
Pang
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CC
D000818:Animals; D004926:Escherichia coli; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy*; D008070:Lipopolysaccharides; D019335:Nitroarginine / Q000494:pharmacology / Q000627:therapeutic use*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013997:Time Factors
D008070:Lipopolysaccharides; D019335:Nitroarginine; D009638:Norepinephrine