scholarly journals Possible genetically determined mechanisms of arterial hypertension in tobacco smoking

Kardiologiia ◽  
2019 ◽  
Vol 59 (1S) ◽  
pp. 4-10
Author(s):  
N. V. Maltseva ◽  
A. Sh. Smirnova ◽  
A. C. Rublevskaya ◽  
N. A. Bichan

Te increase in the prevalence of arterial hypertension (AH) in populations, ineffective treatment, the need for risk stratifcation, prevention, early diagnosis and successful treatment, actualize genomic studies to develop a personalized therapeutic approach to AH. Te review investigates the possible genetically determined mechanisms of the development of hypertension and endothelial dysfunction caused by polymorphism of the genes of endothelial nitric oxide synthase (eNOS) and enzymes of phases I and II of the xenobiotics detoxifcation system. Te probable interaction of both systems under the influence of harmful environmental factors, including tobacco smoking, and in the gestational period is discussed. It is proposed to study AH candidate genes in the xenobiotics detoxifcation system, the carriage of different variants of which can determine the sensitivity or resistance to antihypertensive pharmacotherapy, which can be useful for developing of the personalized tactics of managing patients with AH.

1997 ◽  
Vol 272 (2) ◽  
pp. H806-H813 ◽  
Author(s):  
T. C. Resta ◽  
R. J. Gonzales ◽  
W. G. Dail ◽  
T. C. Sanders ◽  
B. R. Walker

We have previously demonstrated that arterial, but not venous, vasodilatory responses to endothelium-derived nitric oxide (EDNO)-dependent agonists are enhanced in lungs isolated from rats with chronic hypoxia (CH)-induced pulmonary arterial hypertension. These data suggest that CH is associated with increased endothelial nitric oxide synthase (eNOS) activity within the pulmonary arterial vasculature. In addition, the correlation of increased pulmonary arterial pressure with selectively enhanced arterial responsiveness to EDNO-mediated agonists suggests that arterial hypertension, rather than hypoxia per se, is a contributing factor in this response. Therefore, we hypothesized that 1) CH selectively upregulates eNOS within the pulmonary arterial vasculature and 2) monocrotaline (MC)-induced pulmonary arterial hypertension selectively enhances pulmonary arterial dilation to EDNO-dependent dilators and upregulates arterial eNOS. We examined the responses to the EDNO-dependent dilators arginine vasopressin and ionomycin in U-46619-constricted isolated perfused lungs from control and MC-treated rats. Microvascular pressure was assessed by the double-occlusion technique, allowing calculation of segmental resistances. Lungs from MC-treated rats exhibited augmented arterial dilation to arginine vasopressin compared with control lungs. However, the responses to ionomycin were not different between the two groups. Quantitative immunocytochemistry was used to compare pulmonary eNOS immunoreactivity in vessels from control, CH, and MC-treated rats. eNOS staining was more intense in the arteries of CH and MC-treated rats compared with those of control animals, whereas CH and MC treatment had no effect on eNOS staining in veins. We conclude that pulmonary arterial hypertension, or altered vascular mechanical forces associated with hypertension, may be responsible for the augmented EDNO-dependent arterial dilation and upregulation of arterial eNOS in lungs from CH and MC-treated rats.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 585.2-585
Author(s):  
K. Zaichko ◽  
M. Stanislavchuk ◽  
N. Zaichko ◽  
V. Khomenko

Background:One of the most common comorbidity in patients with rheumatoid arthritis (RA) is arterial hypertension (AH), with incidence ranging from 20 to 60%. Mechanisms of this comorbidity arises a lot of interest. In our previous study was established the association ofT786C NOS3(rs2070744) gene polymorphism with AH in females with RA in the Ukrainian population [1].Objectives:So next, we were aiming to investigate daily fluctuation of endothelial nitric oxide synthase (NOS3) in RA patients with AH depending onNOS3 T786Cgene polymorphism.Methods:In the study were enrolled 173 females with RA aged 43.7 ± 7.35 years (Mean ± SD) and 34 age-matched healthy women without joint diseases and autoimmune diseases (control). Serum NOS3 level was determined at 08:00 and 20:00 using Cloud-Clone Corp kits (USA).NOS3 T-786Сpolymorphism was determined by Real-Time PCR (Bio-Rad iCycler IQ5) using SNP-express kit. Study was carried out in compliance with bioethical standards and provisions of the WHO, Helsinki Declaration of the General Assembly of the World Medical Association (1989).Results:Among enrolled patients prevailed individuals with more than 5 years disease history, ІІ-ІІІ radiographic stage (80.9 %), and were seropositive for anti-cyclic citrullinated peptide (80.6%). There were 114 (66%) normotensive patients and 59 (34%) patients with AH (13% - I stage, 20.8% - II stage). The daily fluctuation of NOS3 serum level was established in the control group. The evening NOS3 level was higher in 1.3 times, than the morning level (р<0.001). In RA patients the similar fluctuations of NOS3 level was registered, but the daily NOS3 production was lower, than in control. Diurnal variation of NOS3 level depended on comorbid AH andNOS3 T-786Сgenotype. InCCgenotype NOS3 levels at 08:00 and at 20:00 were lower in 1.2-1.3 times (p<0.05) than inTTandTCgenotypes. In patients with RA and AH the lowest diurnal variation of NOS3 level was inCCgenotype. The decrease of evening NOS3 production was strong associated with comorbid AH (OR 3.78; 95% CI 1.96-7.28).Conclusion:Circadian rhythms of NOS3 production in females with RA and AH depend onNOS3 Т786Сgene polymorphism. The depression of NOS3 production in the evening can be predictor of comorbid AH in females with RA.References:[1]Zaichko, K., & Stanislavchuk, M. (2017, April). T-786C gene promoter polymorphism of endothelial nitric oxide synthase: its association to the disease activity and arterial hypertension in patients with rheumatoid arthritis in the ukraine population. In rheumatology (vol. 56, pp. 129-129). GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND: OXFORD UNIV PRESS.Acknowledgments:NADisclosure of Interests:None declared


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