title: The ruthenium-based nitric oxide scavenger, AMD6221, augments cardiovascular responsiveness to noradrenaline in rats with streptozotocin-induced diabetes.
abstract: Excess production of nitric oxide by inducible nitric oxide synthase (iNOS) has been implicated in cardiovascular dysfunction associated with the acute phase of diabetes mellitus. We examined if the selective nitric oxide scavenger, AMD6221 (ruthenium[hydrogen(diethylenetrinitrilo)pentaacetato] chloride) improved cardiovascular function in rats with streptozotocin (60 mg/kg, i.v.)-induced diabetes. The cardiovascular effects of noradrenaline (16.5 nmol/kg/min, i.v.) were measured in thiobutabarbitone-anaesthetised diabetic and control rats before and after acute administration of AMD6221 (80 mg/kg). Rats in the acute phase of diabetes (3 weeks post injection of streptozotocin) had impaired mean arterial pressure, left ventricular systolic pressure and maximum rate of increase (+dP/dt) and decrease (-dP/dt) of left ventricular pressure responses to noradrenaline compared with control rats. AMD6221 significantly augmented noradrenaline-induced increases in left ventricular systolic pressure and +/-dP/dt in the diabetic but not control rats. The results show that selective scavenging of nitric oxide by AMD6221 improved cardiac response to noradrenaline in rats with streptozotocin-induced diabetes.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, 2176 Heath Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Hutchings
authors.forename: Dongzhe
authors.initials: D
authors.lastname: Song
authors.forename: Simon P
authors.initials: SP
authors.lastname: Fricker
authors.forename: Catherine C Y
authors.initials: CC
authors.lastname: Pang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004357:Drug Synergism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: C453459:AMD 6221; D016166:Free Radical Scavengers; D009942:Organometallic Compounds; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D013311:Streptozocin; D004369:Pentetic Acid; D009638:Norepinephrine