Reversal by L- and D-enantiomers of N-G-nitro-arginine of endotoxin-induced hypotension and vascular hyporesponsiveness

We examined the effects of D-NNA (N-G-nitro-D-arginine) and L-NNA (N-G-nitro-L-arginine) on suppression of Escherichia coli lipopolysaccharide (LPS)induced vascular hyporeactivity in pentobarbital-anesthetized rats. Mean arterial pressure (MAP) and presser 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 presser 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.