The ruthenium-based nitric oxide scavenger, AMD6221, augments cardiovascular responsiveness to noradrenaline in rats with streptozotocin-induced diabetes

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-anaestbetised 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. (c) 2005 Elsevier B.V. All rights reserved.