Experimental Arterial Hypertension Research Articles

Estimation of Renal Clearance in Hypertensive Rats According to fMRI Data.

Renal clearance in Wistar rats with multifactorial cardiovasorenal model of arterial hypertension was assessed by fMRI using (EPI_Diffusion_map) protocol after injection of extracellular contrast agent gadolinium Gd-DTPA. Linear regression analysis was used to assess local concentrations of the contrast agent in the abdominal aorta, kidney compartments, pelvis, and bladder areas. Detection of marker clearance in order to verify the glomerular filtration rate was performed by the RPP (Rutland-Patlak plot) method. In 3 months after hypertension modeling, glomerular filtration rate decreased by 2 times in comparison with the control (31.2±0.44 and 62.3±1.31 μl/min/100 g, respectively; p<0.001). Our findings can indicate the formation of hypertensive nephroangiosclerosis in rats with experimental arterial hypertension. It was found that kidney damage in hypertensive rats is associated with hypofiltration.

Metabolic profile of blood serum in experimental arterial hypertension.

The etiology of essential hypertension is intricate, since it employs simultaneously various body systems related to the regulation of blood pressure in one way or another: the sympathetic nervous system, renin-angiotensin-aldosterone and hypothalamic-pituitary-adrenal systems, renal and endothelial mechanisms. The pathogenesis of hypertension is influenced by a variety of both genetic and environmental factors, which determines the heterogeneity of the disease in human population. Hence, there is a need to perform research on experimental models - inbred animal strains, one of them being ISIAH rat strain, which is designed to simulate inherited stress-induced arterial hypertension as close as possible to primary (or essential) hypertension in humans. To determine specific markers of diseases, various omics technologies are applied, including metabolomics, which makes it possible to evaluate the content of low-molecular compounds - amino acids, lipids, carbohydrates, nucleic acids fragments - in biological samples available for clinical analysis (blood and urine). We analyzed the metabolic profile of the blood serum of male ISIAH rats with a genetic stress-dependent form of arterial hypertension in comparison with the normotensive WAG rats. Using the method of nuclear magnetic resonance spectroscopy (NMR spectroscopy), 56 metabolites in blood serum samples were identified, 18 of which were shown to have significant interstrain differences in serum concentrations. Statistical analysis of the data obtained showed that the hypertensive status of ISIAH rats is characterized by increased concentrations of leucine, isoleucine, valine, myo-inositol, isobutyrate, glutamate, glutamine, ornithine and creatine phosphate, and reduced concentrations of 2-hydroxyisobutyrate, betaine, tyrosine and tryptophan. Such a ratio of the metabolite concentrations is associated with changes in the regulation of glucose metabolism (metabolic markers - leucine, isoleucine, valine, myo-inositol), of nitric oxide synthesis (ornithine) and catecholamine pathway (tyrosine), and with inflammatory processes (metabolic markers - betaine, tryptophan), all of these changes being typical for hypertensive status. Thus, metabolic profiling of the stress-dependent form of arterial hypertension seems to be an important result for a personalized approach to the prevention and treatment of hypertensive disease.

Structural and Functional Changes of the Thoracic Aorta in Experimental Arterial Hypertension

The functional characteristics of the thoracic aorta in Wistar rat with experimental arterial hypertension were studied using MRI. The intravital images of the aorta were obtained using a synchronizer of cardiac and respiratory cycles. The pulse-gradient Turbo-spin-echo sequence and the BODY CARDIAC movie 10 mode were used. The unfavorable factor of increased BP initiated structural and functional changes in the thoracic aorta. At the initial stages, they manifested by an increase of the lumen and a decrease in endothelium-dependent vasodilation. Progression of arterial hypertension (3-6 months) was associated with narrowing of the lumen of both ascending and descending parts of the aorta. Deformation of the aortic arch due to increased density of the vascular wall was observed by the sixth month of the development of arterial hypertension.

Study of possible sex features of ramipril and candesartan treatment under experimental arterial hypertension in rats

The article presents the results of a preclinical study of ramipril and candesartan in an experimental group of hypertensive rats of different sexes. Antihypertensive therapy was performed for 21 days. The drugs were administered daily in moderate therapeutic doses calculated for rats using the coefficient of species sensitivity. It was found that the course of experimental hypertension has gender differences, and in males, according to blood pressure, the level of NO metabolites is more pronounced. The use of ramipril from the group of ACE inhibitors and candesartan from the ARBs group in experimental hypertension in rats has gender differences. Ramipril is likely to be more effective in normalizing blood pressure and endothelial function in males than females. The use of candesartan did not show significant gender differences, but there was a tendency for females to be slightly more effective than males. Established gender differences in hypertension pharmacotherapy should be considered to optimize treatment.

Magnetic Resonance Imaging of Rat Brain in Assessment of the Neuroprotective Properties of Histochrome in Experimental Arterial Hypertension.

The neuroprotective effects of the course therapy with Histochrome in Wistar rats with modeled arterial hypertension were studied by using magnetic resonance imaging (MRI) in diffusion-weighted mode. The behavioral status of the animals was assessed using the open-field test. MRI analysis revealed more pronounced increase in the signaling characteristics of the brain tissue in hypertensive rats in comparison with the control (intact) animals. It was caused by excessive accumulation of fluid in the intra- and extracellular spaces of the brain tissue, which is associated with hypervolemia induced by the multifactorial cardiovasorenal model of hypertension. After a course of Histochrome injections to hypertensive rats, the cerebral microcirculation disorders were leveled, while the behavioral status was characterized by shortened latency of the visit to the center of the open field by 20% and improvement of cognitive activity (by 1.6 times) and the exploratory component (by 30%).

Neurophysiological justification of the G. F. Lang hypothesis about the occurrence of essential hypertension

This article is an analysis of modern data on the morphological, functional and neurochemical organization of the central mechanisms of blood circulation regulation, the violation of which can cause the development of essential hypertension. The data indicating the validity of the hypothesis of G.F. Lang that prolonged emotional stress leads to a violation of the neuronal activity of the hypothalamus structures are presented. The article describes the morphological connections of the hypothalamus with the neurons of the ventrolateral region of the medulla oblongata and the structures of the spinal cord that provide neurogenic vascular tone. The evidence of convergence of axons of neurons of the paraventricular nucleus of the hypothalamus on the preganglionic neurons of the spinal cord is presented. Neurochemical processes in the vasomotor center of the medulla oblongata are considered, morphological changes of preganglionic sympathetic neurons in experimental arterial hypertension are indicated.

Direct comparison of inorganic nitrite and nitrate on vascular dysfunction and oxidative damage in experimental arterial hypertension

Arterial hypertension is one of the major health risk factors leading to coronary artery disease, stroke or peripheral artery disease. Dietary uptake of inorganic nitrite (NO2−) and nitrate (NO3−) via vegetables leads to enhanced vascular NO bioavailability and provides antihypertensive effects. The present study aims to understand the underlying vasoprotective effects of nutritional NO2− and NO3− co-therapy in mice with angiotensin-II (AT-II)-induced arterial hypertension. High-dose AT-II (1 mg/kg/d, 1w, s. c.) was used to induce arterial hypertension in male C57BL/6 mice. Additional inorganic nitrite (7.5 mg/kg/d, p. o.) or nitrate (150 mg/kg/d, p. o.) were administered via the drinking water. Blood pressure (tail-cuff method) and endothelial function (isometric tension) were determined. Oxidative stress and inflammation markers were quantified in aorta, heart, kidney and blood. Co-treatment with inorganic nitrite, but not with nitrate, normalized vascular function, oxidative stress markers and inflammatory pathways in AT-II treated mice. Of note, the highly beneficial effects of nitrite on all parameters and the less pronounced protection by nitrate, as seen by improvement of some parameters, were observed despite no significant increase in plasma nitrite levels by both therapies. Methemoglobin levels tended to be higher upon nitrite/nitrate treatment. Nutritional nitric oxide precursors represent a non-pharmacological treatment option for hypertension that could be applied to the general population (e.g. by eating certain vegetables). The more beneficial effects of inorganic nitrite may rely on superior NO bioactivation and stronger blood pressure lowering effects. Future large-scale clinical studies should investigate whether hypertension and cardiovascular outcome in general can be influenced by dietary inorganic nitrite therapy.

Estimation of the Morphofunctional Status of the Brain in Hypertensive Wistar Rats Using Diffusion-Weighted MRI.

Morphofunctional changes of the brain tissues of Wistar rats were studied based on the development of a multifactor cardiovasorenal model of arterial hypertension using MRI. An increase of the signal on the diffusion brain maps was recorded in 3 months, which indicated fluid accumulation in the intra- and extracellular space of the brain tissue. The data characterize the development of the pathogenetic mechanism of the hypervolemic variant of experimental arterial hypertension. The development of endothelial dysfunction in the brain vessels was manifested by predominance of abnormal constrictor reactions. In 6 months after arterial hypertension simulation, structural changes in the brain developed, such as leukoareosis, cystic encephalomalacia with dilated cerebrospinal fluid spaces and limited blood supply to brain tissue in the basins of the large cerebral arteries.

Pathogenetic features of the nitric oxide system state in the left ventricular myocardium of the rats with experimental arterial hypertension

The aim was to determine the pathogenetic features of the NO system in the myocardium of the left ventricle in the rats with endocrine-salt hypertension.Material and methods. The experiment was conducted on 20 male rats 220-290 g weight, 6–10 months old which were divided into 2 experimental groups: 1st – the control group (10 intact normotensive male Wistar rats); 2nd – 10 male Wistar rats with endocrine-salt arterial hypertension. Systolic and diastolic BP levels were measured in all the rats using a system of non-invasive arterial pressure measurement BP-2000. The objects of study in the experimental animals were blood plasma in which the nitrotyrosine level was measured, and the fragment of left ventricle, which was divided into two parts, one of which was homogenized using a Silent Crusher S homogenizer (Heidolph, Germany), in which nitrites level was determined. Concentration of immunoreactive material to NOS isoforms was detected with immunofluorescence method. The study of NOS mRNA isoforms expression in the left ventricular myocardium homogenates was carried out using a real-time polymerase chain reactionResults. In the experiment, an increase in all 3 isoforms and their mRNA was obtained. In the study, a decrease in nitrites concentration and a significant increase in nitrotyrosine levels, indicates the development of nitroso-oxidative stress.Conclusions. The development of experimental endocrine-salt hypertension in the Wistar rats leads to a stable increase in mean blood pressure by 65 % compared to control. Endocrine-salt arterial hypertension in Wistar rats is characterized by an increased mRNA content of all three isoforms of nNOS, eNOS and iNOS by 2.7, 2.8 and 5.7 times, respectively, compared to the control; increased expression of immunoreactive material to isoforms in transverse fibers by 14.3 %, 16.2 % and 18.5 %, respectively; in longitudinal fibers IRM to nNOS was higher by 8.3 %, to iNOS - by 8. 5%, but to eNOS it was lower by 7.6 %. At the same time, nitrites level decreased by 11.7 % and nitrotyrosine concentration was significantly higher, exceeding the control value by 88.5 %.

Exacerbation of adverse cardiovascular effects of aircraft noise in an animal model of arterial hypertension

Arterial hypertension is the most important risk factor for the development of cardiovascular disease. Recently, aircraft noise has been shown to be associated with elevated blood pressure, endothelial dysfunction, and oxidative stress. Here, we investigated the potential exacerbated cardiovascular effects of aircraft noise in combination with experimental arterial hypertension. C57BL/6J mice were infused with 0.5 mg/kg/d of angiotensin II for 7 days, exposed to aircraft noise for 7 days at a maximum sound pressure level of 85 dB(A) and a mean sound pressure level of 72 dB(A), or subjected to both stressors. Noise and angiotensin II increased blood pressure, endothelial dysfunction, oxidative stress and inflammation in aortic, cardiac and/or cerebral tissues in single exposure models. In mice subjected to both stressors, most of these risk factors showed potentiated adverse changes. We also found that mice exposed to both noise and ATII had increased phagocytic NADPH oxidase (NOX-2)-mediated superoxide formation, immune cell infiltration (monocytes, neutrophils and T cells) in the aortic wall, astrocyte activation in the brain, enhanced cytokine signaling, and subsequent vascular and cerebral oxidative stress. Exaggerated renal stress response was also observed. In summary, our results show an enhanced adverse cardiovascular effect between environmental noise exposure and arterial hypertension, which is mainly triggered by vascular inflammation and oxidative stress. Mechanistically, noise potentiates neuroinflammation and cerebral oxidative stress, which may be a potential link between both risk factors. The results indicate that a combination of classical (arterial hypertension) and novel (noise exposure) risk factors may be deleterious for cardiovascular health.

Effects of short‐term therapy with high dose nutritional inorganic nitrite and nitrate on vascular dysfunction, oxidative damage and epigenetic regulation in experimental arterial hypertension

BackgroundArterial hypertension is one of the major risk factors leading to highly relevant diseases like coronary artery disease, stroke or peripheral artery disease. Even short‐term application of angiotensin‐II (AT‐II) in animal models of arterial hypertension is leading to vascular dysfunction, enhanced production of reactive oxygen species (ROS) and modification of epigenetic processes. Nitric oxide (NO) represents an important opponent to AT‐II induced vasoconstriction and high blood pressure. Dietary uptake (e.g. vegetables) of inorganic nitrite (NO2−) and nitrate (NO3−) leads to enhanced NO bioavailability and provides antihypertensive effects. The present study aims to understand the underlying vasoprotective effects of nutritional NO2− and NO3− co‐therapy in hypertensive mice.Methods and resultsHigh‐dose AT‐II (1mg/kg/d for 1 week) was used to induce arterial hypertension in male C57BL/6 mice. In parallel high dose inorganic nitrite (7.5mg/kg/d) and inorganic nitrate (150mg/kg/d) was administered via drinking water. Hemodynamic effects were evaluated by blood pressure measurements and isometric tension studies. To elucidate underlying epigenetic regulation processes gene expression analyses and quantification of ROS formation were performed.Administration of AT‐II induced hypertension, cardiac hypertrophy and impaired endothelial function. Co‐therapy with high dose inorganic nitrite, but not with nitrate, normalised vascular function and arterial hypertension. In addition, oxidative stress markers and inflammatory pathways were enhanced in hypertensive mice and mostly normalized by nitrite therapy. We observed hypertension induced changes, at least by trend, of epigenetic proteins like histone deacetylase 2 or lysine demethylase 3A in cardiac tissue, which were mostly normalized by nitrite therapy.ConclusionNutritional nitric oxide precursors represent complementary therapy to classical antihypertensive drugs, representing a dietary treatment applicable to the general population (e.g. by eating certain vegetables). Short‐term therapy with inorganic nitrite showed beneficial effects on vascular function, oxidative stress and epigenetic regulation in experimental hypertension, which were less pronounced with inorganic nitrate. The observed differences may rely on superior bioconversion of nitrite to NO or intoxication through methaemoglobinaemia because of high dose inorganic nitrate therapy. Therefore, in particular inorganic nitrite seems to represent a cost‐efficient, drug‐free, alternative in antihypertensive therapy. Further clinical research is necessary to further support these preclinical findings and to demonstrate whether the incidence and severity of hypertension in particular and cardiovascular outcome in general can be influenced by inorganic nitrite therapy.Support or Funding InformationWe gratefully acknowledge the financial support by Stiftung Mainzer Herz (to M.O. and A.D.).

Endothelium-dependent molecular mechanisms of articular cartilage and subchondral bone remodeling in conditions of cardiovascular comorbidity

Aim. To determine the expression level of endothelial factors (VEGF-A, CD34 + ) in the tissues of the joints in experimental arterial hypertension (AH), hyperlipidemia (HL) and their combination. Material and methods . An experimental study was conducted on 24 sexually mature males of outbred guinea pigs. All animals were divided into 4 groups of 6 animals each. In the first group, AH was reproduced by intramuscular injection of a hydrocartisone solution. HL in the second group was simulated by intraperitoneal injection 1 time in 3 weeks of Tween 80 and diet modification. In the third group, the combination of AH and GL was reproduced by injection of a hydrocartisone solution, Tween-80 and diet modification. On the 60-day animals were pull out of the experiment by euthanasia. Hock joint tissue sampling was performed, in which the expression of endothelial vascular growth factor A (VEGF-A), CD34 was determined using a peroxidase immunohistochemical reaction. Results. It was found that during experimental AH, expression of VEGF-A increased in the subchondral bone. In experimental HL, preferential induction of VEGF-A and CD34 in the articular cartilage and subchondral bone is observed. When combined with cardiovascular factors, the highest expression of the molecular mechanisms of cardiometabolic stress, including VEGF-A and CD34 is observed. Conclusion. The results indicate that cardiovascular factors affect the joint tissue. This allows us to make an assumption that the joint tissues belong to the target organs of cardiovascular diseases and make it possible to judge the important role of cardiovascular comorbidity in the pathogenesis of degenerative inflammatory joint diseases.

P4476Cardiovascular benefits of GLP-1 (liraglutide) treatment in experimental arterial hypertension are mediated by the endothelial GLP-1 receptor

Abstract Objective The LEADER trial demonstrated that glucagon-like peptide-1 (GLP-1) analogs like Liraglutide (Lira) reduce the risk of cardiovascular events in T2DM, an effect beyond glycemic control. A detailed evaluation of the precise mechanisms underlying the cardiovascular protective effects of GLP-1 has been hampered by the fact that the GLP-1 receptor is expressed on different cell types in the vasculature including platelets, neuronal, endothelial and inflammatory cells. We used endothelial and myeloid cell-specific knockout mice of the GLP-1 receptor (GLP-1r) in an angiotensin-II (ATII)-induced model of hypertension. The aim of the recent study was to investigate the cardioprotective effects of GLP-1 in ATII-induced arterial hypertension and to characterize the cell-specific contribution of GLP-1r signaling. Methods Arterial hypertension was induced by s.c. ATII administration (0.5mg/kg/d; 7 days) in WT (C57/BL6J) as well as endothelial and myeloid cell-specific GLP-1r knockout mice (Cdh5crexGLP-1rfl/fl and LysMcrexGLP-1rfl/fl mice). Animals were treated with Lira (2x30μg/d; 7 days). Blood pressure was measured by tail-cuff. Vascular function was tested by isometric tension recording. Aortic and cardiac tissue was used for Western blotting, qRT-PCR, FACS, IHC and HPLC to determine the extent of inflammation, oxidative stress and fibrosis. ELISA was used to determine GLP-1 and insulin levels in plasma. Results Endogenous GLP-1 (7–36 and 9–36) was reduced in hypertensive animals. Lira ameliorated blood pressure and improved endothelial dysfunction, vascular oxidative stress and inflammation caused by ATII, in both WT and myeloid cell-specific GLP-1r knockout mice. Hypertension led to infiltration of inflammatory monocytes (Ly6G-Ly6Chigh) and neutrophils (Ly6G+Ly6C+) into the vascular wall, which was prevented by Lira. In accordance, Lira suppressed vascular oxidative stress and mRNA expression of iNOS, CD11b and Nox2. Endothelial NO synthase (eNOS) was S-glutathionylated with ATII treatment indicating uncoupled eNOS. Thus, aortic NO levels were reduced, all of which was restored by Lira. Furthermore, vascular fibrosis and cardiac hypertrophy were tremendously reduced by GLP-1. Interestingly, all of these beneficial cardiovascular effects of GLP-1 were abolished in endothelial cell-specific GLP-1r knockout mice. Conclusion We show that Lira reduces blood pressure and improves vascular function, fibrosis and cardiac hypertrophy in experimental arterial hypertension in mice. Mechanistically, Lira prevents the infiltration of inflammatory cells to the vascular wall, leading to reduced oxidative stress and improved NO bioavailability. Beneficial effects of GLP-1 are mediated by the GLP-1r expressed on endothelial and not myeloid cells. With the present study we provide a mechanistic approach to explain the cardioprotective effects of GLP-1 analogs like Lira, for which the endothelial GLP-1 receptor is indispensable. Acknowledgement/Funding Deutsche Forschungsgesellschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF)

Comparative characteristic of the brain natriuretic peptide and angiotensin II expression index in the structure of locus coeruleus of brain stem in rats with arterial hypertension of various origins

The aim of our study was to determine the characteristics of the BNP and AT II expression in the LC structure of rat brain stem with experimental (genetically determined essential and secondary endocrine-salt) arterial hypertension and to give a comparative description of the expression pattern of these peptides in etiologically different types of arterial hypertension.Materials and methods. The study was carried out on adult 30 male rats. 20 Wistar animals were divided into two groups – control (10 rats) and 10 rats with simulated endocrine-salt AH (ESAH) and 10 rats of the SHR line with essential AH (EAH). The expression parameters of neuropeptides, such as the content, concentration, and relative area of the immunoreactive material, were studied using an immunohistochemical method.Results. It was found that from all BNP expression parameters in the locus coeruleus structure, only relative area increased significantly in both groups. The concentration did not significantly change, and the content of immunoreactive material increased significantly only in animals with ESAH. At the same time, all parameters of angiotensin II expression increased significantly in both experimental groups. Thus, in rats with experimental arterial hypertension in the locus coeruleus structure, more pronounced changes in expression parameters are characteristic for angiotensin II, rather than for BNP. There is a discrepancy between levels of pressor angiotensin II expression and depressor BNP expression in the direction of angiotensin II expression increasing during the arterial hypertension formation. The nature and peculiarities of these neuropeptides expression in the LC structure depend on the key link of the pathogenesis of the modeled arterial hypertension.Conclusions. In rats of the control group with normal blood pressure in LC structure, AT II is more represented. The content and concentration of IRM to AT II are 2.32 and 2.19 times higher than the corresponding BNP values. Prevalence of AT II in the LC structure of the brainstem remains even when arterial hypertension is formed, regardless of its etiology. However, the etiopathogenetic mechanisms of arterial hypertension development impose their own characteristics. In EAH, the content and concentration of AT II is higher than BNP by 4.58 and 3.59 times; in ESAH – by 2.16 and 2.83 times. In the pathogenesis of essential arterial hypertension formation an important role is played by a change in the central control of blood pressure regulation. It is characterized by a significant predominance of the pressor component AT II over the depressor BNP in the brainstem LC structure.

Magnetic Resonance Imaging in Assessment of Cardiac Remodeling in Rats with Experimental Arterial Hypertension.

Magnetic resonance imaging was employed to examine the morphofunctional status of myocardium in Wistar rats with multifactor cardiovasorenal model of arterial hypertension. In 3 months after the onset of experiment, the rats demonstrated a pronounced hypertrophy in left ventricular myocardium mostly due to thickening of the posterior and lateral walls against the background of relatively stable thickness of ventricular septum. The left ventricular endsystolic volume markedly increased in parallel with moderate increase of the end-diastolic volume. The standard calculated indices were used for precise assessment of the type of remodeling of individual myocardial structures. The study showed that multifactor arterial hypertension model was characterized by domination of hypertrophic mode of the left ventricular remodeling, whereas the concentric variant was observed more rarely by 2.5 times. The greatest alterations were observed in the posterior and lateral walls of the left ventricle, which could result from the hemodynamic effects of hypervolemic arterial hypertension.

Morphometric and densitometric characteristics of the brainstem locus coeruleus neurons nuclei in rats with experimental arterial hypertension

The aim of our study was to establish the morphodensitometric features of locus coeruleus (LC) neurons nuclei in the brain stem of rats with arterial hypertension of various origin (essential – SHR and endocrine-salt hypertension (ESH)).Matherials and methods: the study was carried out on 30 mature male rats: 10 control Wistar rats, 10 Wistar rats with modeled endocrine-salt AH (ESH) and 10 spontaneously hypertensive rats (SHR) with genetically determined hypertension. The histochemical method of staining with gallocyanine-chrome alum by Einarson was used for the evaluation of morphodensitometric characteristics of the neurons nuclei: the nucleus area, the content and concentration of nucleic acids (NA) in the nucleus.Results: it was found that the highest indices were observed in rats of the SHR line while in rats with ESH the content, RNA concentration and nucleus area decreased. In SHR rats with essential hypertension high synthetic activity was observed in the LC neurons with an increase of the content and concentration of NA.Conclusions. Morphometric and densitometric characteristics of the of the brain stem LC in AH depend on the etiological factor and pathogenesis of hypertension. In essential AH of SHR there is a high synthetic activity in the brainstem LC neurons nuclei along with an increase in the content and concentration of NA. In symptomatic AH in rats with ESH, on the contrary, the structure activity is decreased and characterized by the reduction in nucleus size and NA content in it.

Molecular and cellular mechanisms of osteoarthritis in experimental arterial hypertension and hyperlipidemia

Purpose: To study the role of vascular endothelial growth factor (VEGF-A), adiponekin (Adipo) and matrix metalloproteinase-9 (MMP-9) in remodeling of articular cartilage (AC) and subchondral bone (SCB) in experimental arterial hypertension (AH) and hyperlipidemia (HL). Methods: An experimental study was carried out on 18 adult males of purebred guinea pigs (28-30 weeks old, weight 750-900 g), which were divided into 3 groups of 6 individuals each: in the first group AH was modeled, in the second group - HL, the third group was intact animals (control). To assess the reproduction of a qualitative model in animals, the level of blood pressure, total cholesterol, and body weight were determined. On the 60th day all the animals were removed from the experiment, the tissues of the knee joints of the hind (hock) paws were taken. Immunohistochemical reaction was performed according to the standard protocol using primary species-specific antibodies to VEGF-A, Adipo, MMP-9. Results: In the control group of animals, the immunohistochemical reaction of AC to VEGF-A was determined as single low-intensity precipitates in the region of the pericellular matrix of the basal layers of chondrocytes. In the SCB, single precipitates of vascular endothelial growth factor were found in the central parts of the haversian systems. A high intensity response to VEGF was observed in the red bone marrow. In the group of animals with hypertension, the reaction of articular cartilage on VEGF-A was determined in all areas of cartilage. Its greatest intensity was in the perchondrium, on the periphery of the zones of destruction of the articular cartilage. Within the limits of the fuzzy osteochondral line, elements of ectopic vascular invasion were determined by the type of non-vascular expansion in AC with a positive response to VEGF. Maximum expression of VEGF-A was found in the region of contact of the subchondral bone with destruction of articular cartilage. In hyperlipidemia, AC was positive for VEGF-A in the area of chondrocyte lacunae of hypertrophied chondrocytes in all layers of the cartilage plate. In SCB, the vascular endothelial growth factor was found in the area of osteogenesis imperfecta foci, the red bone marrow. The histochemical reaction of AC and SCB to adiponectin in intact animals was practically not determined. There were isolated low-intensity precipitates. Tissue expression of Adipo in animals with AH in AC was determined in the form of multiple precipitates with a high density of IHC-reaction with a maximum response in the basal regions of the cartilage plate. In the SCB with experimental hypertension, adiponectin tissue precipitates were found in the area of haversian systems, osteochondral communication. In hyperlipidemia in AC, a positive reaction to Adipo was found in the area of chondrocyte lacunae predominantly in the upper and middle layers of the cartilage plate. in all layers of the cartilage plate. Under conditions of lipid metabolism impairment, the Adipo SCB was defined as diffuse deposits in the communicative regions with basal soreness, in the zones of the haversian systems and the bone matrix. The tissue response to MMP-9 SCB and AC in the control group was not very pronounced, showing up as single low-intensity cell-cell precipitates. Under the conditions of experimental arterial hypertension in the articular cartilage, MMP-9 was determined in the subcellular matrix of hypertrophied chondrocytes, mainly in the middle layer. In SCB, a positive response to matrix metalloproteinase-9 was found in the area of angiovasal integration into the basal cartilage, in the centers of imperfect osteogenesis. The highest expression density of MMP-9 was determined in the group of animals with HL. Deposits of MMP-9 were found in cartilage tissue, mainly in the upper and middle sections. In SCB at HL, the tissue reaction to the matrix metalloproteinase-9 was also detected in the foci of ectopic angiogenesis. Conclusions: The results of the study allowed to establish that under the influence of systemic AH and HL in the articular cartilage and subchondral bone cell stress develops, caused by endothelium-dependent dysmetabolism. In the present study, it was shown that extravasal expression of VEGF-A is observed in experimental AH, most pronounced in SCB. In addition, moderate expression of adiponectin and MMP-9 in the SCB is noted. In systemic AH, in experimental conditions, VEGF-A is overexpressed in articular cartilage. In addition to this, in addition to this, Adipo and MMP-9 are highly expressed in SCB. It is established that angiogenic factors contribute to the neovascularization of cartilage, non-adaptive osteoregeneration of SCB. At the same time, remodeling of the tissues of the joints is obviously provided by tissue metalloproteinases. The data obtained allow us to makethe assumption that SCB and AC are target organs of cardiovascular factors.

THE RELATIONSHIP BETWEEN THE SEASON OF THE YEAR AND THE VASORENAL HYPERTENSION OCCURRENCE

Objective. The aim of this work was to study the impact of seasons on the incidence of the experimental arterial hypertension. Design and methods . We applied the model of vasorenal hypertension “2 kidney, 1 clip” in Wistar male rats in standard laboratory conditions. We compared the following parameters in the groups with clipped arteries in autumn, winter and spring: systolic blood pressure, beat-to-beat interval, low- and high-frequency components of heart rate variability. Results. The risk of vasorenal hypertension occurrence was higher in spring (56 %). More seldom vasorenal hypertension developed in winter (20 % of animals), and an increase in density of low and high-frequency components of heart rate variability was observed after applying renal artery clamp in the winter group. There was a clear correlation between an increase in the average monthly variability of atmospheric pressure and a decrease in the frequency of vasorenal hypertension occurrence. Conclusions. We conclude that the season has an impact on the development of hypertension, which probably is due to the seasonal changes in sympathetic and parasympathetic activity. We assume that clear seasonal dynamics of atmospheric pressure variability causes the seasonal variations in the functioning of the cardiovascular and autonomic nervous systems in standard laboratory conditions.

Changes in Tripeptidyl Peptidase II Activity in Aortic Tissues under Experimental Atherosclerosis and Arterial Hypertension

Changes in Tripeptidyl Peptidase II Activity in Aortic Tissues under Experimental Atherosclerosis and Arterial Hypertension

The Involvement of a Polyphenol-Rich Extract of Black Chokeberry in Oxidative Stress on Experimental Arterial Hypertension

The aim of this study is to characterize the content of Aronia melanocarpa Elliott (black chokeberry) extract and also to estimate the influence of polyphenolic compounds contained in chokeberries on oxidative stress, on an L-NAME-induced experimental model of arterial hypertension. The rat blood pressure values were recorded using a CODA Noninvasive Blood Pressure System. HPLC/DAD coupled with ElectroSpray Ionization-Mass Spectrometry allowed identification of five phenolic compounds in berries ethanolic extract as follows: chlorogenic acid, kuromanin, rutin, hyperoside, and quercetin. The serous activity of glutathione-peroxidase (GSH-Px) has significantly lower values in the hypertensive (AHT) group as compared to the group protected by polyphenols (AHT + P). The total antioxidant capacity (TAC) values are lower in the AHT group and they are significantly higher in the AHT + P group. All the measured blood pressure components revealed a biostatistically significant blood pressure drop between the AHT group and the AHT + P group. The results reveal the normalization of the reduced glutathion (GSH) concentration as well as a considerable reduction in the malondialdehyde (MDA) serum concentration in the AHT + P group. Ethanolic extract of black chokeberry fruits not only has a potential value as a prophylactic agent but also may function as a nutritional supplement in the management of arterial hypertension.