Neuroprotective Activity of D-HES in Transient Global Cerebral Ischemia in Rats.

We studied the effect of O-((((4-hydroxy-3,5-di(1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl) benzyl)oxy)ethyl)-O-(2-hydroxyethyl)-(1→4)-α-D-glucan (D-HES, 80 mg/kg, intravenously) and reference preparation ethylmethylhydroxypyridine succinate (EMHP-S, 50 mg/kg, intravenously) on rat survival and neurological deficit in 24 h after transient global cerebral ischemia in Wistar rats. Intravenous administration of D-HES and EMHP-S significantly increased the number of survivors by 68 and 78%, respectively, in comparison with the control group. In groups treated with D-HES and EMHP-S, the number of animals with severe neurological deficit was significantly lower and the number of animals moderate or mild neurological deficit was significantly higher than in the control group.

Dihydroquercetin Improves Microvascularization and Microcirculation in the Brain Cortex of SHR Rats during the Development of Arterial Hypertension.

The effects of dihydroquercetin (50 mg/kg intragastrically daily for 6 weeks) on the density of capillary network (mean number of capillaries per mm2), mean capillary diameter, structure of capillary network, capillary diameter distribution (<3, 3-5, 5-7, and 7-9 µ), and local cerebral blood flow (by laser Doppler) in the visual cortex were studied in SHR rats during the development of arterial hypertension (from the 6th to the 12th week of life). Normally, the systolic and diastolic BP progressively increased in SHR rats during this period. Dihydroquercetin did not affect the development of arterial hypertension. At the same time, the drug significantly increased the mean diameter of capillaries (by 11%), capillary network density (by 23%), and in the percentage of capillaries with a diameter of 3-9 µ (passable for erythrocytes; by 42%). Positive effects of dihydroquercetin on the structure of microcirculatory bed improved microcirculation: local cerebral blood flow in the visual cortex of SHR rats was significantly higher (by 36%) than in rats receiving no flavonoid and close to the value in Wistar-Kyoto rats. Dihydroquercetin improved microvascularization and microcirculation in the cerebral cortex of SHR rats during the formation of arterial hypertension.

Modes of Hypotensive Action of Dihydroquercetin in Arterial Hypertension.

We studied the effect of dihydroquercetin (20 mg/kg/day intragastrically for 6 weeks) on mean BP and macro- and microrheological blood parameters in hypertensive SHR rats; in vitro effect of dihydroquercetin on the tone in thoracic aorta rings isolated from hypertensive SHR rats were also examined. At the end of the treatment course, the mean BP in the experimental rats decreased by 11%; the left ventricular mass index by 2%, and whole blood viscosity by 7-10% in comparison with control SHR rats; erythrocyte aggregation half-time increased by 15%; plasma viscosity, hematocrit, and erythrocyte deformability did not change. In in vitro experiments, dihydroquercetin (10-8-10-6M) induced relaxation of the isolated thoracic aorta rings in a dose-dependent manner. Hence, the antihypertensive effect of dihydroquercetin results from the decrease in blood viscosity and vasodilation.

[Specificity of the Hemodynamic Indices' Shift in SHR Line Rats at Different Age].

Specificities of the changes in the systemic hemodynamics indices in the spontaneously hypertensive line SHR rats have been studied in comparison with the normotensive line WKY rats. It was demonstrated that an increase in blood pressure observed in the young hypertensive male rats, which have completed puberty (8 weeks old), is associated with the development of the hyperkinetic type arterial hypertension, which is characterized by increased cardiac minute output. It has been shown that SHR line male rats reveal the establishment of stable arterial hypertension due to a significant increase in the total peripheral resistance with the simultaneous recovery of the cardiac minute output by the 25th week of life. SHR line rats at the age of 15 weeks may be regarded as being in the period of transition from the hyperkinetic type arterial hypertension to stable arterial hypertension.

[EFFECT OF CAPTOPRIL ON THE ARTERIAL PRESSURE AND RHEOLOGICAL PROPERTIES OF BLOOD, THE VASODILATOR ACTIVITY OF ENDOTHELIUM, AND RELATIONSHIP OF THESE INDICES IN SHR RATS.]

Prevention of cardiovascular complications is one of the objectives of antihyperiensive therapy. However, the expected effect cannot be fully achieved by me- ans of the blood pressure control only. The authors studied the effect of captopril administration in SHR rats by monitoring the following parameters: arterial blood pressure, rheological properties of blood, and endothelial index of vasodilator activity (IVA), as well as their correlations. In SHR rats, the systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher by 28 - 33% as compared to WKY rats. In comparison to normotensive animals, the blood vis- cosity (BV) at shear rates from 30 to 450 sec -1 in SHR rats was increased by 12 - 15% (p = 0.020), the aggregation of red blood cells was increased by 22% (p = 0.012), and their plasticity in the range of shear stresses within 3 - 20 Pa was decreased by 2 - 8% (p = 0.028). The IVA value in SHR rats was lower by 26 % (p = 0.030) than that in WKY rats. The administration of captopril decreased the SBP and DBP values down to the level in normotensive animals, but did not influence the rheological properties of blood and its IVA value. In WKY rats, the BV exhibited reliable correlation with IVA (with r from +0.60 ai +0.67, p <0.05) at shear rates ranging within 30 - 450 sec -1, while the rheological parameters were correlated with neither SBP nor DBP. In SHR rats, the BV corre- lated with IVA only at 450 sec -1 (with r =+0.50, p = 0.025), and there were relationships between SBP and BV (r = + 0.64, p = 0.008) and the aggregation in- dex (r = +0.69, p = 0.003). Rats treated with captopril showed no correlations between hemorheological and hemodynamic parameters. Therefore, captopril decreases the arterial blood pressure, but it also violates the contour of vascular tone regulation associated with changes in shear stress on the vascular wall, which plays an important role in ensuring adequate local blood flow.

Quantitative Indexes of Leukocytes in Spontaneously Hypertensive Rats During Various Periods of Arterial Hypertension Development.

SHR rats were examined in the period before arterial hypertension development (5th week), during the increase in BP (6th-10th weeks), and under conditions of constantly elevated BP (11th-12th weeks). The total number of leukocytes did not differ in SHR and normotensive WKY rats. However, the relative number of lymphocytes and monocytes was shown to differ in various periods of arterial hypertension development. Our results suggest that white blood cells (primarily lymphocytes) are involved in the development of arterial hypertension.

Dynamics of Blood Pressure Elevation and Endothelial Dysfunction in SHR Rats During the Development of Arterial Hypertension.

The dynamics of systolic and diastolic BP and vasodilatory activity of the endothelium in SHR and Wistar-Kyoto rats was studied from the 5th to the 12th week of life. Systolic and diastolic BP did not differ in 5-week-old SHR and Wistar-Kyoto rats. After the 6th week of life, two stages of arterial hypertension development were observed in SHR. Stage 1 (weeks 6-8) was characterized by a significant increase in systolic and diastolic BP that exceeded the corresponding parameters in Wistar-Kyoto rats by 26-32%. Vasodilatory activity of the endothelium was similar in rats of both strains at the age of 5-7 weeks. Stage 2 (weeks 9-12) in SHR rats was characterized by further increase in systolic and diastolic BP that exceeded the corresponding parameters in Wistar-Kyoto rats by 54-89%. The increase in BP during this period was accompanied by a significant decrease in endothelium-dependent relaxation (by 14-16% compared to that in Wistar-Kyoto rats of the same age).

[PARAMETERS OF CEREBRAL CORTEX CAPILLARY NETWORK IN SHR RATS DURING THE DEVELOPMENT OF ARTERIAL HYPERTENSION AND STABLE HIGH BLOOD PRESSURE].

The studies were performed in hypertensive rats (SHR strain) during the period of hypertension development (7-8 weeks) and stable high blood pressure (16-17 weeks) and in normotensive rats (WKY strain) of corresponding ages. The average number of capillaries per square millimeter, the average capillaries diameter, and the capillary network structure following the estimation of capillaries distribution based on capillaries diameter within the following ranges (up to 3, from 3 to 5, from 5 to 7 and from 7 to 9 µm) were investigated using the morphological approach. The average diameter of capillaries and capillary network structure in SHRs during the development of hypertension did not differ from the respective values in WKY rats of the same age. SHR rats showed disturbed microvascularisation by structural and functional rarefaction in the stable high blood pressure period, which was manifested in lower average capillaries density and average capillaries diameter as well as in substantial (2.5 times) increase in plasmatic capillaries as compared to WKY rats of the same age.

[DYNAMICS OF BLOOD PRESSURE AND QUANTITY INDICES OF ERYTHROCYTES IN SHR IN EARLY PERIOD OF ARTERIAL HYPERTENSION FORMING].

The dynamics of arterial blood pressure and hematological parameters (RBC volume, RBC count, hematocrit) in young rats SHR and WKY strains in the period from the 5th to the 8th week after birth was investigated. At the age of 5 weeks, the levels of arterial blood pressure in rats studied strains were not significantly different. Starting from 6 weeks, systolic and diastolic blood pressure in SHR rats were significantly higher than the corresponding values of WKY rats of the same age. During the entire period of observation (from the 5th to 8th week) the number of red blood cells and hematocrit in SHR rats was significantly increased compared with the value of these parameters in WKY rats. Probably, an increased hematocrit can be one of the reasons of increasing the blood pressure in the early stages of hypertension development.