Nitric oxide‐mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock
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Discussion
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Implication
Animal study reveals biphasic nitric oxide release drives vascular hyporeactivity in septic rats, indicating constitutive enzyme activation precedes inducible synthase expression.
Key Points
- To investigate the relative roles of constitutive and inducible nitric oxide synthase in the onset of early and delayed vascular hyporeactivity to noradrenaline during endotoxin shock.
- Anaesthetized male Wistar rats received an intravenous bolus of Escherichia coli lipopolysaccharide (10 mg/kg) to induce circulatory shock, with continuous tracking of mean arterial blood pressure and heart rate.
- Vascular responses to intravenous noradrenaline (0.3, 1, or 3 µg/kg) and organ-specific calcium-dependent versus calcium-independent nitric oxide synthase activities were measured with or without L-NAME (1 mg/kg) or dexamethasone (3 mg/kg).
- Lipopolysaccharide induced an immediate, sustained fall in mean arterial blood pressure within 5 minutes and significantly reduced noradrenaline pressor responses at 30 and 60 minutes, which L-NAME fully reversed while dexamethasone had no effect.
- Inducible, calcium-independent nitric oxide synthase activity appeared only moderately in the aorta at 60 minutes but rose significantly across the lung, liver, spleen, mesentery, heart, and aorta by 180 minutes.
- Pretreatment with dexamethasone prevented both the delayed systemic hypotension and the noradrenaline hyporeactivity observed at 180 minutes by suppressing tissue nitric oxide synthase induction.
Cite This Study
Szabó et al. (1993) studied this question.