[Effect of adaptation to hypoxia on expression of NO synthase isoforms in rat myocardium].

Previously we have shown that adaptation to hypoxia (AH) is cardio- and vasoprotective in myocardial ischemic and reperfusion injury and this protection is associated with restriction of nitrosative stress. The present study was focused on further elucidation of NO-dependent mechanisms of AH by identifying specific NO synthases (NOS) that could play the major role in AH protection. AH was performed in a normobaric hypoxic chamber by breathing hypoxic gas mixture (9.

[Antiarrhythmic effect of oligonucleotides accompanied by activation of HSP70 protein in the heart of rats].

Unlabelled: The mechanisms of the protective effect of oligonucleotides (OGN) during pathological processes are poorlyunderstood. The goal of this work was to study the effect of OGN on arrhythmias induced by myocardial ischemia and reperfusion, and the HSP70 level in the heart. As a source of OGN was used the drug "Derinat" ("Technomedservis", Russia).

Effect of Nitric Oxide Synthesis Blockade on the Morphology of Langerhans Islets in August and Wistar Rats with Acute Alloxan Diabetes.

Alloxan diabetes was modeled in August rats with high activity of the NO system and in Wistar rats, and the effects of NO system blockade (by a course treatment with L-NNA) on Langerhans islet β cells were studied in 15 days. The toxic effects of diabetes on the rat β cells and islets were similar: the content of active β cells in the islets decreased to 15-20%, the number of islets to 24-29% of control. A course of L-NNA reduced the β cell and islet death, in August cells greater than in Wistar: the number of islets in August rats was restored to 81%, in Wistar rats to 60% of initial level; the activity of β cells remained at the control level in the former and 2-fold lower than in the control in the latter.

[Effect of NO-synthesis blockade on the free-radical processes in rats of different genetic strains with acute alloxan diabetes].

Previously, we have shown that nitric oxide (NO) plays an important role in the pathogenesis of alloxan diabetes (ALD). In this study in August rats, with the congenital increased activity of NO, and in Wistar rats was induced ALD (130 mg/kg, p/c) and 15 days after were examined the effects of the NO-blockade synthesis, induced by administration of Nω-nitro-L-arginine (L-NNA) cour- se on the activity of lipid peroxidation (LP), HIF-1α level, the degree of NO-system activation. The activation of iNOS, HIF-1a expression and 3-nitrotyrosine accumulation in liver were more pronounced in August-ALD rats than in Wistar-ALD rats.

[Vasoprotective effect of adaptation to hypoxia in myocardial ischemia and reperfusion injury].

Adaptation to hypoxia is known to be cardioprotective in ischemic and reperfusion (IR) injury of the myocardium. This study was focused on investigating a possibility for prevention of endothelial dysfunction in IR injury of the rat heart using adaptation to intermittent hypoxia, which was performed in a cyclic mode (5-10 min of hypoxia interspersed with 4 min of normoxia, 5-8 cycles daily) for 21 days. Endothelial function of coronary blood vessels was evaluated after the in vitro IR of isolated heart (15 min of ischemia and 10 min of reperfusion) by the increment of coronary flow rate in response to acetylcholine.

Normobaric, intermittent hypoxia conditioning is cardio- and vasoprotective in rats.

Favorable versus detrimental cardiovascular responses to intermittent hypoxia conditioning (IHC) are heavily dependent on experimental or pathological conditions, including the duration, frequency and intensity of the hypoxia exposures. Recently, we demonstrated that a program of moderate, normobaric IHC (FIO2 9.5-10% for 5-10 min/cycle, with intervening 4 min normoxia, 5-8 cycles/day for 20 days) in dogs afforded robust cardioprotection against infarction and arrhythmias induced by coronary artery occlusion-reperfusion, but this protection has not been verified in other species.

Role of nitric oxide in the pathogenesis of alloxan diabetes.

We studied the effects of N(w)-nitro-L-arginine (L-NNA), a nonselective inhibitor of NO synthases, on the severity of type 1 diabetes mellitus induced by subcutaneous injection of 130 mg/kg alloxan in August rats with high activity of NO system and in Wistar rats. Five days after alloxan injection, hyperglycemia levels after overnight fasting in August and Wistar rats were 27.1±3.

[Role of restricted nitric oxide overproduction in the cardioprotective effect of adaptation to intermittent hypoxia].

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.

Effect of acute alloxan diabetes on ischemic and reperfusion arrhythmias in rats with different activity of nitric oxide system.

Similar degree of glycemia (28-31 mmol/liter) and similar mortality (37-42%) were revealed in August rats exhibiting enhanced activity of NO system and in Wistar rats 3 weeks after alloxan treatment. Under conditions of myocardial ischemia caused by 10-min coronary artery ligation, the intensity of arrhythmias did not differ from the control in Wistar rats with diabetes mellitus and increased in August rats. Under conditions of reperfusion, diabetes produced an antiarrhythmic effect in Wistar rats and did not affect arrhythmia in August rats.

[Particularities of adrenergic regulation and the function of cardiovascular system at remote periods after myocardial infarction in rats of different strains].

Unlabelled: Heart function was studied in the August rats with innate raised sympathetic-adrenal system and in the Wistar rats through the period of 3 month after myocardial infarction. The sizes of the postinfarction scars were similar in the rats under comparison (56-62%) but end-diastolic pressure in Wistar rats and in August rats was 18.7 +/- 2.

Adaptation of the cardiovascular system to postinfarction cardiosclerosis in rats with congenital adrenoreactivity of the myocardium.

Three months after myocardial infarction the severity of heart failure and size of postinfarction scars in August rats with inherently reduced adrenoreactivity of the myocardium were similar to those in Wistar rats. The mortality rate in August rats was 2.5-fold lower than in Wistar rats.

Antiarrhythmic effect of heat adaptation in ischemic and reperfusion injury to the heart.

Study on a model of 6-day dosed adaptation to heat in rats showed that this adaptation decreased the severity of cardiac arrhythmias during ischemic and reperfusion injury. The duration of arrhythmias decreased not only in the ischemic period, but also under conditions of reperfusion. Adaptation delayed the development of arrhythmias during ischemia, decreased the number of animals with late reperfusion arrhythmias, and improved recovery of the heart after ischemia and reperfusion.

Peculiarities of autonomic regulation assessed by variability of hemodynamic parameters in rats with different stress resistance.

Analysis of contribution of sympathetic and parasympathetic systems into heart rate variability carried out using atenolol and atropine showed that August rats are characterized by enhanced tone of the sympathetic system and reduced tone of the parasympathetic system compared to Wistar rats. Reduced tone of the parasympathetic system is also confirmed by lower sensitivity of the baroreflex. Blockade of NO synthesis with Nw-nitro-L-arginine more markedly increased blood pressure variability in August rats compared to Wistar rats.

[Variability of hemodynamic parameters and resistance to stress damage in rats of different strains].

Total power of heart rate variability and baroreflex sensitivity were significantly smaller in the August rats than in the Wistar rats, but adrenal and plasma catecholamine contents were considerably higher in the former ones. 1 hour after stress (30 min in cold water), plasma catecholamine was increased 2-fold in Wistar rats, while in August rats the adrenaline concentration increased only by 58% and the were no changes in noradrenaline content. At the same time, activation of catecholamine metabolism in the adrenal glands was similar in both groups.

Heart resistance to oxidative stress in rats of different genetic strains.

In August rats reperfusion after regional myocardial ischemia in situ or intracoronary administration of hydrogen peroxide less significantly suppressed contractile activity of the heart compared to Wistar rats. Activities of catalase and superoxide dismutase in the myocardium during reperfusion remained unchanged in August rats. In Wistar rats a profound inhibition of cardiac function was accompanied by a decrease in enzyme activity.

[Contractile function of the heart and myocardium antioxidant system in rats of August and Wistar strains during ischemia and reperfusion].

In August rats, local myocardial ischemia caused by 30-min occlusion of the coronary artery induced a slight depression of the contractile function of the heart; the latter was restored after 15-min reperfusion more rapidly than in Wistar rats. In August rats, the activities of antioxidant protection enzymes were lower than in Wistar rats. In comparison with Wistar rats, these enzyme activities were decreased in a lesser degree under ischemia and were restored in a greater degree under reperfusion.

Effect of stress on variability of systemic hemodynamics in rats of various genetic strains.

Power spectral density of heart rate fluctuations in the range of 0.02-5.00 Hz in August rats was lower than in Wistar rats.

August rats are more resistant to arrhythmogenic effect of myocardial ischemia and reperfusion than Wistar rats.

As differentiated from Wistar rats, myocardial ischemia and reperfusion produce no ventricular fibrillation in August rats. Pretreatment with nitric oxide synthase inhibitor Nw-nitro-L-arginine increased mortality rate in August rats with acute myocardial infarction from 20 to 40%. Under these conditions mortality rate in Wistar rats increased from 50 to 71%.

[The role of stress proteins HSP70 and the adrenergic system in different resistance to myocardial infarction of August and Wistar genetic rat strains].

A lesser resistance against myocardial infarction (MI) in the Wistar rats as compared with the August rats was found to be combined with a greater stress-response and activation of the heart sympathetic regulation in the former rats. In the Wistar rats and not in August rats, an activation of hypothalamic noradrenaline (NA) system occurs as well as a greater "output" of the NA from sympathetic terminals in the myocardium. Accumulation of the HSP 70 stress-proteins in IM in the myocardium is nearly 2-2.

HSP70 stress proteins, nitric oxide, and resistance of August and Wistar rats to myocardial infarction.

Accumulation of HSP70 stress proteins in the myocardium and blood content of nitrite/nitrate in August rats with modeled myocardial infarction surpassed these parameters in Wistar rats less resistant to cardiovascular disorders by 2-2.5 and 1.8 times, respectively.

Genetically determined differences in the resistance to myocardial infarction in Wistar and August rats.

In intact August rats, the cardiac contractile function at rest was by 76% higher than in Wistar rats, while their hearts, both intact and after acute myocardial infarction, were more resistant to isometric load than the hearts of Wistar rats. Postinfarction mortality in August rats was 18% vs. 70% in Wistar rats.

[The cardioprotective action of the anticonvulsant preparation sodium valproate in disorders of cardiac contractile function caused by acute myocardial infarct in rats].

The preventive and therapeutical effects of sodium valproate (SV), 200 mg/kg, on cardiac contractile disorders (developed pressure, rate-pressure products, dp/dt) were studied in rats having 2-day myocardial infarction (MI). The postinfarction rather than preinfarction use of SV substantially restricted the depressed resting left ventricular function. Given by two regimens, SV increased cardiac resistance to the maximum isometric load induced by 60-sec ligation of the ascending aorta.