Oral N(G)-nitro-L-arginine in conscious dogs: 24 hour hypertensive response in relation to plasma levels

Haemodynamic changes after oral administration of 30 mg/kg N(G)-nitro-L-arginine (L-NNA) were studied in conscious chronically instrumented mongrel dogs throughout a 24 h observation period in order to evaluate the long-term efficacy of L-NNA-induced inhibition of endothelium-dependent relaxation and its relation to plasma L-NNA level. Diastolic blood pressure remained elevated for the entire 24 h observation period, but systolic blood pressure was raised only up to the 6 h value. The hypertensive response was accompanied by bradycardia. The increase in blood pressure and the plasma L-NNA level both reached their maxima at 3 h. The plasma L-NNA level at the end of the observation period was diminished by only 21.7% with respect to the maximum increase, whilst the maximum increase in mean arterial blood pressure was attenuated by 72.2% at 24 h. These data show a dissociation between plasma L-NNA level and the respective blood pressure.