The Nitric Oxide Metabolite Level and NOS2 and NOS3 Gene Transcripts in Patients with Essential Arterial Hypertension

Abstract

It was shown that the level of nitric oxide metabolites in the blood plasma of people with essential arterial hypertension (EAH) is significantly higher than that of healthy donors. This pattern did not depend on the stage of the disease, but on the age of the subjects, as well as on whether patients with cardio-selective β-adrenoreceptor blockers take them or not. It was established that an increase in the level of nitrites and nitrates in the blood of patients with EAH was accompanied by an increase in the level of transcripts of the NOS2 gene in the peripheral blood leukocytes (PBL), while the mRNA content of the NOS3 gene in the PBL patients was slightly lower than that of healthy donors.

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REFERENCES

  1. 1

    Bauersachs, J., Bouloumie, A., Mulsch, A., Wiemer, G., Fleming, I., and Busse, R., Vasodilator dysfunction in aged spontaneously hypertensive rats: changes in NO synthase III and soluble guanylyl cyclase expression, and in superoxide anion production, Cardiovasc. Res., 1998, vol. 37, pp. 772–779.

    CAS  Article  Google Scholar 

  2. 2

    Bautista, L.E., Vera, L.M., Arenas, I.A., and Gamarra, G., Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-α) and essential hypertension, J. Hum. Hypertens., 2005, vol. 19, pp. 149–154.

    CAS  Article  Google Scholar 

  3. 3

    Crabos, M., Coste, P., Paccalin, M., Tariosse, L., Daret, D., Besse, P., and Bonoron-Adele, S., Reduced basal NO-mediated dilation and decreased endothelial NO-synthase expression in coronary vessels of spontaneously hypertensive rats, J. Mol. Cell. Cardiol., 1997, vol. 29, pp. 55–65.

    CAS  Article  Google Scholar 

  4. 4

    Diagnosis and treatment of hypertension. Russian recommendations (IV revision). Russian Medical Society of Arterial Hypertension. All-Russia Scientific Society of Cardiology, Sist. Gipertenz., 2010, no. 3, pp. 5–26.

  5. 5

    Dias, F.A., Urboniene, D., Yuzhakova, M.A., Biesiadecki, B.J., Pena, J.R., Goldspink, P.H., Geenen, D.L., and Wolska, B.M., Ablation of iNOS delays cardiac contractile dysfunction in chronic hypertension, Front. Biosci. (Elite Ed.), 2010, vol. 2, pp. 312–324.

  6. 6

    Förstermann, U. and Sessa, W., Nitric oxide synthases: regulation and function, Eur. Heart J., 2012, vol. 33, pp. 829–837.

    Article  Google Scholar 

  7. 7

    Ghasemi, A., Zahedi Asl, S., Mehrabi, Y., Saadat, N., and Azizi, F., Serum nitric oxide metabolite levels in a general healthy population: relation to sex and age, Life Sci., 2008, vol. 83, pp. 326–331.

    CAS  Article  Google Scholar 

  8. 8

    Ginnan, R., Guekema, B.J., Halligan, K.E., Singer, H.A., and Jourd’heuil, D., Regulation of smooth muscle by inducible nitric oxide synthase and NADPH oxidase in vascular proliferative disease, Free Radic. Biol. Med., 2008, vol. 44, pp. 1232–1245.

    CAS  Article  Google Scholar 

  9. 9

    Godecke, A., Decking, U.K., Ding, Z., Hirchenhain, J., Bidmon, H.J., Godecke, S., and Schrader, J., Coronary hemodynamics in endothelial NO synthase knockout mice, Circ. Res., 1998, vol. 82, pp. 186–194.

    CAS  Article  Google Scholar 

  10. 10

    Habib, S. and Ali, A., Biochemistry of nitric oxide, Ind. J. Clin. Biochem., 2011, vol. 26, pp. 3–17.

    CAS  Article  Google Scholar 

  11. 11

    Heusch, P., Aker, S., Boengler, K., Deindl, E., van de Sand, A., Klein, K., Rassaf, T., Konietzka, I., Sewell, A., Menazza, S., Canton, M., Heusch, G., Di Lisa, F., and Schulz, R., Increased inducible nitric oxide synthase and arginase II expression in heart failure: no net nitrite/nitrate production and protein S-nitrosylation, Am. J. Physiol. Heart Circ. Physiol., 2010, vol. 299, pp. 446−453.

    Article  Google Scholar 

  12. 12

    Higashino, H., Miya, H., Mukai, H., and Miya, Y., Serum nitric oxide metabolite (NOx) levels in hypertensive patients at rest: a comparison of age, gender, blood pressure and complications using normotensive controls, Clin. Exp. Pharmacol. Physiol., 2007, vol. 34, pp. 725–731.

    CAS  Article  Google Scholar 

  13. 13

    Hong, H.-J., Loh, S.-H., and Yen, M.-H., Suppression of the development of hypertension by the inhibitor of inducible nitric oxide synthase, Br. J. Pharmacol., 2000, vol. 131, p. 631–632.

    CAS  Article  Google Scholar 

  14. 14

    Kumar, U., Chen, J., Sapoznikhov, V., Canteros, G., White, B.H., and Sidhu, A., Overexpression of inducible nitric oxide synthase in the kidney of the spontaneously hypertensive rat, Clin. Exp. Hypertens., 2005, vol. 27, pp. 17–31.

    CAS  Article  Google Scholar 

  15. 15

    Levy, A.S., Chung, J.C.S., Kroetsch, J.T., and Rush, J., Nitric oxide and coronary vascular endothelium adaptations in hypertension, Vasc. Health Risk Manage., 2009, vol. 5, pp. 1075–1087.

    CAS  Google Scholar 

  16. 16

    Lowenstein, C.J., Dinerman, J.L., and Snyder, S.H., Nitric oxide: a physiologic messenger, Ann. Int. Med., 1994, vol. 120, pp. 227–237.

    CAS  Article  Google Scholar 

  17. 17

    Lyamina, N.P., Dolotovskaya, P.V., Lyamina, S.V., Malyshev, I.Y., and Manukhina, E.B., Nitric oxide production and intensity of free radical processes in young men with high normal and hypertensive blood pressure, Med. Sci. Monit., 2003, vol. 9, pp. CR304–CR310.

    CAS  PubMed  Google Scholar 

  18. 18

    Lyusov, V.A., Metel’skaya, V.A., Oganov, R.G., Evsikov, E.M., and Teplova, N.V., The level of nitric oxide in peripheral blood serum of patients with varying severity of hypertension, Kardiologiya, 2011, no. 12, pp. 23–28.

  19. 19

    Metel’skaya, V.A. and Gumanova, N.G., The screening method for determining the level of nitric oxide metabolites in blood serum, Klin. Lab. Diagn., 2005, no. 6, pp. 15–18.

  20. 20

    Mokuno, S., Ito, T., Numaguchi, Y., Matsui, H., Toki, Y., Okumura, K., and Hayakawa, T., Impaired nitric oxide production and enhanced autoregulation of coronary circulation in young spontaneously hypertensive rats at prehypertensive stage, Hypertens. Res., 2001, vol. 24, pp. 395–401.

    CAS  Article  Google Scholar 

  21. 21

    Nava, E., Noll, G., and Luscher, T.F., Increased activity of constitutive nitric oxide synthase in cardiac endothelium in spontaneous hypertension, Circulation, 1995, vol. 91, pp. 2310–2313.

    CAS  Article  Google Scholar 

  22. 22

    Pacher, P., Beckman, J.S., and Liaudet, L., Nitric oxide and peroxynitrite in health and disease, Physiol. Rev., 2007, vol. 87, pp. 315–424.

    CAS  Article  Google Scholar 

  23. 23

    Piech, A., Massart, P.E., Dessy, C., Feron, O., Havaux, X., Morel, N., Vanoverschelde, J.L., Donckier, J., and Balligand, J.L., Decreased expression of myocardial eNOS and caveolin in dogs with hypertrophic cardiomyopathy, Am. J. Physiol. Heart Circ. Physiol., 2002, vol. 282, pp. H219–H231.

    CAS  Article  Google Scholar 

  24. 24

    Rush, J.W., Denniss, S.G., and Graham, D.A., Vascular nitric oxide and oxidative stress: determinants of endothelial adaptations to cardiovascular disease and to physical activity, Can. J. Appl. Physiol., 2005, vol. 30, pp. 442–474.

    CAS  Article  Google Scholar 

  25. 25

    Santulli, G., Adrenal signaling in heart failure something more than a distant ship’s smoke on the horizon, Hypertension, 2014, vol. 63, pp. 215–216.

    CAS  Article  Google Scholar 

  26. 26

    Santulli, G., Ciccarelli, M., Trimarco, B., and Iaccarino, G., Physical activity ameliorates cardiovascular health in elderly subjects: the functional role of the b adrenergic system, Front. Physiol., 2013, vol. 4, p. 209.

    Article  Google Scholar 

  27. 27

    Schulz, S., Schagdarsurengin, U., Suss, T., Müller-Werdan, U., Werdan, K., and Gläser, C., Relation between the tumor necrosis factor-a (TNF-a) gene and protein expression, and clinical, biochemical, and genetic markers: age, body mass index and uric acid are independent predictors for an elevated TNF-a plasma level in a complex risk model, Eur. Cytokine Netw., 2004, vol. 15, pp. 105–111.

    CAS  PubMed  Google Scholar 

  28. 28

    Smith, C.J., Santhanam, L., Bruning, R.S., Stanhewicz, A., Berkowitz, D.E., and Holowatz, L.A., Upregulation of iNOS contributes to attenuated cutaneous vasodilation in essential hypertensive humans, Hypertension, 2011, vol. 58, pp. 935–942.

    CAS  Article  Google Scholar 

  29. 29

    Vaziri, N.D., Ni, Z., Oveisi, F., and Trnavsky-Hobbs, D.L., Effect of antioxidant therapy on blood pressure and no synthase expression in hypertensive rats, Hypertension, 2000, vol. 36, pp. 957–964.

    CAS  Article  Google Scholar 

  30. 30

    de Vera, M.E., Shapiro, R.A., Nussler, A.K., Mudgett, J.S., Simmons, R.L., Morris, S.M., Jr., Billiar, T.R., and Geller, D.A., Transcriptional regulation of human inducible nitric oxide synthase (NOS2) gene by cytokines: initial analysis of the human NOS2 promoter, Proc. Natl. Acad. Sci. U. S. A., 1996, vol. 93, pp. 1054–1059.

    CAS  Article  Google Scholar 

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Funding

This study was supported by the federal budget for performance of a state assignment of the Federal Research Center, Karelian Research Center, Russian Academy of Sciences, project no. 0221-2017-0049.

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Correspondence to L. V. Topchieva.

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

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Translated by P. Vikhreva

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Topchieva, L.V., Balan, O.V., Korneva, V.A. et al. The Nitric Oxide Metabolite Level and NOS2 and NOS3 Gene Transcripts in Patients with Essential Arterial Hypertension. Biol Bull Russ Acad Sci 47, 247–252 (2020). https://doi.org/10.1134/S1062359020010161

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