title: Regional and cardiac haemodynamic effects of NG, NG,dimethyl-L-arginine and their reversibility by vasodilators in conscious rats.
abstract: 1. A series of experiments was carried out on 3 separate groups of male Long Evans rats, chronically instrumented for the measurement of regional haemodynamics, to compare the effects of NG,NG, dimethyl-L-arginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA), and their reversibility by the nitric oxide donors, S-nitroso-N-acetyl-penicillamine (SNAP), S-nitroso-glutathione (SNOG), sodium nitroprusside (SNP), and the vasodilator, hydralazine. 2. As previously reported for L-NMMA, ADMA (1-100 mg kg-1) caused dose-dependent pressor and bradycardic effects, accompanied by renal, mesenteric and hindquarters vasoconstrictions. The magnitude and duration of these effects were similar for ADMA and L-NMMA, consistent with their being equipotent inhibitors of nitric oxide synthase. 3. Infusion of SNAP or SNOG (300 micrograms kg-1 h-1) after injection of ADMA or L-NMMA (100 mg kg-1) reversed the pressor but did not abolish the vasoconstrictor, effects of ADMA or L-NMMA. However, a higher dose of SNAP (3 mg kg-1 h-1) caused complete reversal of the pressor and mesenteric haemodynamic effects of ADMA (100 mg kg-1), although its renal and hindquarters vasoconstrictor effects were not abolished. 4. Infusion of SNP (300 micrograms kg-1 h-1) after administration of L-NMMA (100 mg kg-1), caused complete reversal of its pressor and mesenteric and hindquarters haemodynamic effects, and reduced substantially its renal vasoconstrictor action; hydralazine (7.5 mg kg-1 h-1) was almost as effective as SNP in reversing all these variables. 5. In animals chronically instrumented for the measurement of cardiac haemodynamics, ADMA(100 mg kg-1) caused a pressor effect accompanied by a rise in central venous pressure, and reductions in heart rate, cardiac index, stroke index, peak aortic flow, maximum rate of rise of aortic flow and total peripheral conductance. The reversal of the pressor effect of ADMA by SNAP (300 microg kg-1 h-1) was accompanied by a reduction of central venous pressure below resting levels and a further diminution of stroke index; all other variables showed an increase, but they still remained below resting levels (with the exception of heart rate).6. Thus, following inhibition of NO synthesis, pharmacological intervention with NO donors, or other vasodilators, may cause normalisation of the mean arterial pressure without necessarily returning all associated cardiovascular variables to normal.
authors.affiliation: Department of Physiology & Pharmacology, University of Nottingham Medical School, Queen's Medical Centre.
authors.forename: S M
authors.initials: SM
authors.lastname: Gardiner
authors.forename: P A
authors.initials: PA
authors.lastname: Kemp
authors.forename: T
authors.initials: T
authors.lastname: Bennett
authors.forename: R M
authors.initials: RM
authors.lastname: Palmer
authors.forename: S
authors.initials: S
authors.lastname: Moncada
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine; D026422:S-Nitrosoglutathione; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine
chemical_list: D009603:Nitroso Compounds; D014665:Vasodilator Agents; D009599:Nitroprusside; D006830:Hydralazine; D019323:omega-N-Methylarginine; D026422:S-Nitrosoglutathione; C018524:N,N-dimethylarginine; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D005978:Glutathione; D010396:Penicillamine