Reversal by L- and D-Enantiomers of NG-Nitro-Arginine of Endotoxin-Induced Hypotension and Vascular Hyporesponsiveness

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Abstract
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.