scholarly journals Renin-angiotensin-aldosterone system in ISIAH rats with stressinduced arterial hypertension

2016 ◽  
Vol 20 (6) ◽  
pp. 954-958 ◽  
Author(s):  
A. D. Dubinina ◽  
E. V. Antonov ◽  
L. A. Fedoseeva ◽  
E. N. Pivovarova ◽  
A. L. Markel ◽  
...  
2018 ◽  
Vol 31 (10) ◽  
pp. 542 ◽  
Author(s):  
Ana Célia Sousa ◽  
Roberto Palma dos Reis ◽  
Andreia Pereira ◽  
Sofia Borges ◽  
Ana Isabel Freitas ◽  
...  

Introduction: Arterial hypertension is a complex, multifactorial disease, controlled by genetic and environmental factors.Objective: Evaluate the genetic susceptibility for developing arterial hypertension and its association with the traditional risk factors in the outbreak of this pathology.Material and Methods: Case-control study with 1712 individuals, mean age of 51.0 ± 7.9 years (860 hypertensive patients and 852 controls). Biochemical and traditional risk factors, and genetic variants were evaluated: ACE I/D rs4340, ACE A2350G rs4343, AGT T174M rs4762, AGT M235T rs699 AGTR1 A1166C rs5186, CYP11B2 -344 C/T rs1799998, ADRB1 R389G rs1801253, ADRB2 R16G rs1042713, ADD1 G460W rs4961, SCNN1G G173A rs5718, GNB3 C825T rs5443, ATP2B1 A/G rs2681472, CYP17A1 T/C rs11191548, SLC4A2 C/T rs2303934. The risk of each gene for hypertension was estimated by the dominant, recessive, co-dominant and multiplicative models. By logistic regression, variables associated with hypertension were evaluated. ROC curves were first performed with traditional risk factors and then adding the genetic variants associated with hypertension. Data were analyzed by SPSS for Windows 19.0 and MedCalc v. 13.3.3.0.Results: The genetic variants ADD1 G460W, GNB3 C825T, ACE I/D, ACE A2350G were associated with hypertension. ROC curve with traditional risk factors and these variants showed an increase in the predictive capacity of hypertension (p = 0.018).Discussion: According to the results of our study, the genetic variants found to be associated with hypertension were: ACE I/D rs4340, ACE A2350G rs4343, ADD1 G460W rs4961 and GNB3 C825T rs5443. The first two variants are associated with hypertension by interfering with the renin-angiotensin-aldosterone system, which plays an important role in regulating blood pressure. It should be noted that genes encoding the components of renin-angiotensin-aldosterone system are natural candidates for the development and progression of hypertension. In our population alpha-aducin polymorphism (ADD1 G460W rs4961) was also associated with hypertension. In a Portuguese population, known to have high salt intake, it makes sense that this polymorphism which is relevant in salt and water management may consequently be relevant in the onset of hypertension. The genetic variant GNB3 C825T rs5443 that affects intracellular signalling was also found to be a strong risk candidate for hypertension. Initially, with the elaboration of the ROC curve and calculation of the AUC using only with traditional risk factors and later by adding the variants ADD1 G460W, GNB3 C825T, ACE I/D and ACE A2350G to the traditional risk factors, we verified that genetic polymorphisms increased the predictive risk of hypertension, when compared to the risk given only by traditional risk factors, with statistical significance (p = 0.018). This suggests that hypertension is a multifactorial disease that results from the interaction of environmental, genetic and lifestyle factors that interact with each other and lead to the advent of this important pathology.Conclusion: In our study, the hypertension-associated polymorphisms are linked to the renin-angiotensin-aldosterone axis (ACE I/D, ACE A2350G), as well as to salt and water management (ADD1 G460W, GNB3 C825T). Through a multivariate analysis, it was concluded that these two last genetic variants together with four of the traditional risk factors (smoking, alcohol consumption, obesity and diabetes) are associated in a significant and independent way with essential hypertension. In a predictive model of hypertension, the introduction of genetic variants slightly increases the predictive value of the model.


2021 ◽  
Vol 93 (9) ◽  
pp. 1125-1131
Author(s):  
Valery I. Podzolkov ◽  
Anna Е. Bragina ◽  
Yulia N. Rodionova ◽  
Galina I. Bragina ◽  
Ekaterina E. Bykova

Results of foreign and Russian studies indicate a higher mortality rate of patients with concomitant cardiovascular diseases (CVD) due to the new coronavirus infection COVID-19. It has been proven that arterial hypertension, as one of the significant risk factors for the development of concomitant cardiovascular diseases, is associated with a more severe prognosis of COVID-19. This article presents the results of modern studies and large meta-analyzes of necessity and safety of the use of blockers of the renin-angiotensin-aldosterone system in patients with arterial hypertension and COVID-19. The data of studies show that an angiotensin-converting enzyme inhibitor (ACE inhibitor) and a thiazide-like diuretic is a pathogenetically rational combination. It realizes various ways of lowering blood pressure by reducing the activity of the renin-angiotensin-aldosterone system, which is achieved by using an ACE inhibitor, and natriuresis due to diuretics. As an example, a highly effective fixed combination of drugs is considered, characterized by good tolerance, which consists of an ACE inhibitor lisinopril and a thiazide-like diuretic indapamide of prolonged action. The authors expressed the opinion that the appointment of the fixed combination drug Diroton Plus (Gedeon Richter) will contribute to effective control of blood pressure and organoprotection in conditions of increased thrombogenic and prooxidative potential, characteristic of COVID-19 both in the acute stage and within the post-COVID Syndrome.


2020 ◽  
Vol 11 (3) ◽  
pp. 16-21
Author(s):  
Anna V. Logatkina ◽  
Viktor S. Nikiforov ◽  
Stanislav S. Bondar' ◽  
Igor' V. Terekhov ◽  
Vladimir K. Parfeniuk

In the pathogenesis of arterial hypertension (AH), the renin-angiotensin-aldosterone system plays a key role in helping to maintain elevated blood pressure. At the same time, the state of angiotensin-II production (AT II) and the expression level of its receptors on target cells determine the formation of most of the effects underlying the pathogenesis of associated clinical conditions in such patients. Thus, the study of the pathogenesis of AH, namely the study of the role of the AT II axis, the AT II receptor, is an actual scientific and practical task. Aim. Given the important role of type 1 receptors for AT II in the formation of pathological changes in arterial hypertension, the purpose of this study was to study the peculiarities of the effect of their expression on biochemical processes in patients with arterial hypertension. Material and methods. In the course of the clinical study, 60 patients of both sexes with hypertension aged 45 to 55 years old were admitted to the clinic for planned treatment. Depending on the initial level of expression of receptors for AT II (AT1R), determined by the serum concentration of the soluble form of type 1 receptors for AT II, the patients were divided into two subgroups with conditionally low (corresponding to the concentration of the soluble form of the receptor for AT II 0.66 ng/ml) and conditionally high (1.57 ng/ml) expression. The analysis showed that high expression of AT1R is associated with elevated plasma levels of renin by 30.8% (p=0.0005), AT II by 48.1% (p=0.00001), E-selectin by 47.9% (p=0.0001), VCAM-1 by 29.1% (p=0.00001), ICAM-1 by 52.9% (p=0.00001), VE-cadherin by 50.9% (p=0.00001), endothelin-1 by 48.8% (p=0.0005), an ACE inhibitor by 13.6% (p=0.047), and CRP by 74.1% (p=0.00002 ) and endoperoxide by 29.7% (p=0.009). Against this background, there was a decrease in the level of apoA1 by 21.6% (p=0.027), ACE by 20.1% (p=0.1), the level of antioxidants by 22.3% (p=0.00001). The analysis showed that in the group with initially high expression of AT1R, there was an increased blood pressure, the level of which, on average, exceeded the values of patients with low expression of the indicated receptor by 24.5 mm Hg (p=0.011). Against the background of therapy in the group with high expression of AT1R, plasma renin activity decreased by 20.3% (p=0.013), endoperoxide by 8.4% (p=0.038), an ACE inhibitor by 14.6% (p=0.02). At the same time, the level of apoA1 increased by 8.5% (p=0.036), antioxidants by 8.6% (p=0.036), ICAM-1 by 5.3% (p=0.05), VE-cadherin by 2.5% (p=0.07). The level of the remaining factors was not statistically significant. In the subgroup with low expression of the AT II receptor, during treatment, there was a decrease in endoperoxide by 12.8% (p=0.031), an ACE inhibitor by 5.5% (p=0.044) without significant changes in other indicators. Conclusion. In hypertensive patients, higher expression of AT1R is associated with high activation of immune-inflammatory mechanisms, dyslipidemia, an imbalance of the lipid peroxidation system and antioxidant protection, as well as higher renin-angiotensin-aldosterone system activity and increased arterial pressure. On the background of antihypertensive therapy, partial compensation of the identified changes is achieved, including a moderate increase in the level of antioxidants, a decrease in the concentration of endoperoxide, renin activity and an increase in the level of apoA1, while maintaining an increased level of AT II, high expression of receptors to it. These changes indicate the need for further search for effective antihypertensive therapy strategies aimed at limiting the activity of renin-angiotensin-aldosterone system in patients with hypertension.


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