RELATIONSHIP BETWEEN IMPAIRED GLOBAL LEFT VENTRICULAR DEFORMITY AND NITROXIDE-PRODUCING ENDOTHELIAL FUNCTION IN HYPERTENSIVE PATIENTS

One  of  the  mechanisms  of  development  of  heart  failure  in  patients  with  hypertension  with impaired relaxation of the left ventricle is a change in the nitroxide-producing function of the endothelium.

Objective:  to  study  the  global  longitudinal  deformation  of  the  left  ventricle  and  signs  of  endothelial dysfunction in violation of diastolic relaxation of the left ventricle in patients with hypertension.

Materials and methods. 221 patients with stage 1-2 hypertension (103 women and 118 men) were examined, the average age was 42±9.4 years. The control group consisted of 86 healthy individuals. The material for the genetic study was 221 DNA samples. A polymerase chain reaction was performed with the detection of the amplification product. The frequency of genotypes of nitric oxide synthase type 3 in the NOS3 C786E gene was studied. The endothelin content was studied using an ELISA kit from Eagle Biosciences.Inc. The global deformation was determined by the method of non-Doppler mode of gray-scale deformation. 

Results. In patients with hypertension in combination with impaired relaxation of the left ventricle, the genotype of SS nitrogen synthase was 2 times more common than in healthy individuals and 1.5 times more common  than  in  patients  with  hypertension  without  diastolic  dysfunction  (p=0.0076  and  p=0.0042, respectively). The amount of nitrites and nitrates was lower in the group of patients with hypertension in combination with diastolic dysfunction by 52% compared to the control and by 13% compared to the group of  patients  without  DD.  These  changes  are  interrelated  with  a  decrease  in  the  global  longitudinal deformation of the left ventricle. The correlation analysis revealed a moderate negative relationship between the global longitudinal deformation of the left ventricle and the content of NO3 (r=0.64, p=0.004), the presence  of  a  moderate  negative  correlation  between  the  MMLF  index  and  the  concentration  of  NO2 (r=0.54, p=0.047).

Conclusion. In patients with hypertension, in combination with a violation of diastole, a decrease in the function of the endothelium was revealed, which is interrelated with a decrease in the global deformation of the left ventricle.

1. Guidelines for the diagnosis and treatment of acute and chronic heart failure 2016 ESC. European Journal of Heart Failure. 2016. 18. 883–1084.

2. Zimnitskaya O.V., Petrova M.M. Features of endothelial dysfunction in hypertension. Medical Alphabet. 2019. 3 (1): 29-33. in Russian.

3. Koch N.V., Slepukhina A.A., Lifshits G.I. Arterial hypertension: molecular genetic and pharmacological approaches. Pharmacogenetics and pharmacogenomics. 2015. 2. 4-8. in Russian.

4. Vatutin N.T., Sklyannaya E.V. Endothelial dysfunction as a risk factor of arterial hypertension progression. The Siberian Medical J. 2017. 32 (4): 23-7. in Russian.

5. Napoli C., Ignarro L.J. Nitric oxide and pathogenic mechanisms involved in the development of vascular diseases. Arch Pharm Res. 2009. 32 (8): 1103-8. doi:10.1007/s12272-009-1801-1.

6. Versari D., Daghini E., Virdis A., et al. Endothelium-dependent contractions and endothelial dysfunction in human hypertension. Br J Pharmacol. 2009. 157 (4): 527-36. doi:10.1111/j.1476-5381.2009.00240.x.

7. Shimbo D., Muntner P., Mann D. et all. Endothelial dysfunction and the risk of hypertension: the multi-ethnic study of atherosclerosis. Hypertension. 2010. 55 (5): 1210-6. doi:10.1161/HYPERTENSIONAHA.109.143123.

8. Lytsy P., Lind L., Sundström J. Endothelial function and risk of hypertension and blood pressure progression: The prospective investigation of the vasculature in Uppsala seniors. Journal of Hypertension. 2013. 31 (5): 936-9. doi:10.1097/HJH.0b013e32835ed5a0.

9. Tang E.H., Vanhoutte P.M. Endothelial dysfunction: a strategic target in the treatment of hypertension? Pflugers Arch. 2010. 459 (6): 995-1004. doi: 10.1007/s00424-010-0786-4.

10. Bleakley C., Hamilton P.K., Pumb R., et all. Endothelial Function in Hypertension: Victim or Culprit? J Clin Hypertens (Greenwich). 2015. 17 (8): 651-4. doi:10.1111/jch.12546.

11. Аlekhin M.N. Problems and prospects of echocardiographic evaluation of left ventricular diastolic function. Cardiology. 2017. 57 (1). 71-75. in Russian.

12. Kalinkina T.V., Lareva N.V., Chistyakova M., Gorbunov V.V. The relationship of endothelial dysfunction with the development of diastolic heart failure in patients with hypertension patients. Rational Pharmacotherapy in Cardiology. 2020. 16 (3): 370-376. https://doi.org/10.20996/1819-6446-2020-05-04/ in Russian.