title: 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-1 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 2 min 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.
authors.affiliation: Department of Experimental Pharmacology, Via Domenico Montesano, Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Sorrentino
authors.forename: A
authors.initials: A
authors.lastname: Pinto
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D005730:Ganglionic Blockers / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy; D007275:Injections, Intravenous; D008297:Male; D008760:Methylguanidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D014511:Uremia / Q000188:drug therapy
chemical_list: D005730:Ganglionic Blockers; D018738:Hexamethonium; D008760:Methylguanidine; D001120:Arginine; D019001:Nitric Oxide Synthase