Search

We have previously shown that the innate increased activity of the NO- system, typical for the August rats, increases vulnerability to alloxane diabetes (ALD). The purpose of this study was to investigate the effect of ALD on the cardiovascular system and lipid peroxidation in rats with different activity of NO-system. The August rats and Wistar rats treated with alloxan (125 mg/kg, s/c, once) were studied 3.5 months after. In August-ALD the double production significantly decreased to a greater extent (by 35%) than in Wistar-ALD (by 17%) compared with the control. As in August-ALD and in Wistar-ALD was observed the similar fall of the relaxation (-dp/dt) of the left ventricle (by 45-49%), but not the contraction rate (+dp/dt). LPO activation in the heart and liver, as well as NO-system (level of nitrates and nitrites in the blood plasma) in August rats were more pronounced than in Wistar rats. The hsp32 level in August rats fell significantly more (by 93% ) than in Wistar rats (by 61%). Pathological changes in the microvasculature of the mesostenium were identical in compared rats. Thus, more pronounced cardiac dysfunction in August-ALD, compared with Wistar-ALD, associated with greater activation of lipid peroxidation and NO-system.

Adaptation to intermittent normobaric hypoxia is cardioprotective and can stimulate nitric oxide (NO) synthesis. However the role of nitric oxide (NO) in prevention of ischemia-reperfusion (IR) injury of myocardium is controversial. This study was focused on evaluating the effect of adaptation to hypoxia and IR on NO production and development of nitrative stress in the myocardium. Adaptation to hypoxia tended to increase NO production, which was determined by the total level of plasma nitrite and nitrate, and prevented IR-induced NO overproduction. The IR-induced NO overproduction was associated with significant 3-nitrotyrosine (3-NT) accumulation in the left ventricle but not in septum or aorta. In hypoxia-adapted rats, 3-NT after IR was similar to that of control rats without IR. IHC induced marked accumulation of HIF-1alpha in the left ventricle. We suggest that HIF-1alpha contributes to NO-synthase expression during adaptation to hypoxia and thereby facilitates the increase in NO production. NO, in turn, may subsequently prevent NO overproduction during IR by a negative feedback mechanism.