Effect of methylguanidine on rat blood pressure: role of endothelial nitric oxide synthase

Abstract

1 The effect of acute i.v. administration of methylguanidine (MG) on mean arterial blood pressure (MABP) was investigated in anaesthetized male Wistar rats. 2 MG (1–30 mg kg^−l i.v.) produced an increase in MABP in a dose-dependent manner both in normal and in hexamethonium (5 mg kg⁻¹, i.v)-treated rats. 3 L-Arginine (30 or 150 mg kg⁻¹, i.v.), but not its enantiomer D-arginine (30 or 150 mg kg⁻¹, i.v.), reversed the effect of MG on MABP in both normal and hexamethonium-treated rats. 4 L-Arginine (150 mg kg⁻¹, i.v.) administered 2min before MG (30 mg kg⁻¹, i.v.) prevented the increase in MABP caused by MG in either normal or hexamethonium-treated rats. This effect was not observed with D-arginine (150 mg kg⁻¹, i.v.). 5 Thus, the rise in MABP caused by MG in the anaesthetized rat is due to inhibition of endothelial NO-synthase activity. We speculate that the rise in the plasma concentration of endogenous MG associated with uraemia may contribute to the hypertension seen in patients with chronic renal failure.