RESUMEN
OBJECTIVES: To investigate the effect of acetylcholine (ACh) and ischaemia/reperfusion injury on functional changes and dysrhythmias of the isolated diabetic rat heart. METHODS AND RESULTS: On retrogradely perfused hearts isolated from 10-week-old diabetic rats (streptozotocin 30 mg/kg b.w. for three consecutive days i.p.), two types of experiments were done: /1/ The effect of acetylcholine (ACh; 3 x 10(-7) mol/l) was evaluated both during and after infusion, and /2/ the influence of the ischaemia/reperfusion injury (I/R) was studied. At the end of both experiments the hearts were electrically stimulated to evoke sustained ventricular fibrillation (VF). An increase of coronary arterial pressure, bradycardia and decreased total number of severe dysrhythmias of both types, spontaneous and evoked ones, were recorded in the diabetic hearts. ACh increased the force of contraction (LVP) and induced vasoconstriction, which persisted in the diabetic hearts even after removal of ACh from the perfusion solution. CONCLUSIONS: The isolated diabetic rat heart was more resistant against severe dysrhythmias. After washing out the ACh, the vasoconstriction of coronary arteries still lasted, along with increased inotropic effect on the left ventricle.
Asunto(s)
Acetilcolina/farmacología , Diabetes Mellitus Experimental/patología , Corazón/efectos de los fármacos , Isquemia Miocárdica/patología , Daño por Reperfusión/patología , Estreptozocina , Acetilcolina/uso terapéutico , Animales , Diabetes Mellitus Experimental/complicaciones , Angiopatías Diabéticas/complicaciones , Angiopatías Diabéticas/patología , Potenciales Evocados/efectos de los fármacos , Masculino , Isquemia Miocárdica/complicaciones , Ratas , Ratas Wistar , Daño por Reperfusión/complicaciones , Vasodilatadores/farmacología , Fibrilación Ventricular/patologíaRESUMEN
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) profiles of eye lens proteins showed that both progression of diabetic cataract in rats in vivo and precipitation of soluble eye lens proteins stressed by free radicals in vitro were accompanied by significant protein cross-linking. There was a noticeable contribution of disulfide bridges to protein cross-linking in diabetic eye lens in vivo. In contrast, under conditions in vitro, when eye lens proteins were exposed to hydroxyl or peroxyl radicals, we showed that the participation of reducible disulfide linkages in the formation of high molecular mass products was markedly lower. These in vivo--in vitro differences indicate that the generally accepted role of reactive oxygen species in diabetic cataractogenesis may be overestimated in connection with the processes of protein cross-linking.