Stress and arterial hypertension: ISIAH rat strain. Ye. V. Antonov, Yu. V. Alexandrovich, A. A. Seryapina, L. O. Klimov, A. L. Markel


The main views of the issue of stress and hypertension are briefly reviewed. It is well known that stress is one of the major risk factors for cardiovascular disease development. Increase in blood pressure is a typical manifestation of the acute stress response. This fact is the reason to hypothesize that chronic stress causes the development of hypertensive disease. An association of hypertension with psychological stress in humans was shown in several works. In addition, it was demonstrated that hypertension was accompanied by an increase in sympathetic tone. On the other hand, there were many population studies in which no association was found between different types of chronic stress and arterial hyper­tension. Thus, the question is far from being answered. Even in the cases when one managed to obtain a signi­ficant hypertensive effect in experimental studies with emotional stress, it was difficult to explain the mechanisms mediating the formation of stressinduced hypertension. To clarify the situation, one of the authors of this review decided to begin the breeding of a rat strain with increased blood pressure response to emotional stress. This breeding gave rise to inbred rats with persistent stress-induced arterial hypertension. A brief history of the development of the genetic model ofstress-induced arterial hypertension, the ISIAH rat strain, is given. A retrospective review of the studies performed with ISIAH rats is presented. The contribution of genotype changes in the neuroendocrine systems involved in stress and blood pressure regulation to the development ofstress-dependent hypertension in the ISIAH rat strain is shown.

About The Authors:

Ye. V. Antonov. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

Yu. V. Alexandrovich. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

A. A. Seryapina. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

L. O. Klimov. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

A. L. Markel. Institute of Cytology and Genetics SB RAS; Novosibirsk State University, Russian Federation, Novosibirsk


1. Adarichev V.A., Korokhov N.P., Ostapchuk Ia.V., Dymshits G.M., Markel A.L. Characterization of rat lines with normotensive and hypertensive status using genomic fingerprinting. Genetika — Genetics (Moscow). 1996; 32(12):1669-1672.

2. Amstislavsky S., Welker P., Fruhauf J.H., Maslova L., Ivanova L., Jensen B., Markel A.L., Bachmann S. Renal and endocrine changes in rats with inherited stress-induced arterial hypertension (ISIAH). Histochem. Cell Biol. 2005;8:1-9.

3. Antonov Ye.V., Markel A.L., Jacobson G.S. Aldosterone and the stressdependent hypertension. Byulleten eksperimentalnoy biologii i meditsiny — Bull. Experim. Biol. Med. 2011;152(8):148-151.

4. Antonov Ye.V., Moreva T.A., Cherkasova O.P., Gilinsky M.A., Markel A.L., Jacobson G.S. Adrenal cortex secretory activity in hypertensive ISIAH rat strain. Byulleten SO RAMN — Bull. SD RAMS. 2010;30(4):68-75.

5. Caspi A., Harrington H., Moffitt T.E., Milne B.J., Poulton R. Socially isolated children 20 years later: risk of cardiovascular disease. Arch. Pediatr. Adolesc. Med. 2006;160:805-811.

6. Chida Y., Steptoe A. Greater cardiovascular responses to laboratory mental stress are associated with poor subsequent cardiovascular risk status: a meta-analysis of prospective evidence. Hypertension. 2010;55:1026-1032.

7. Cozier Y., Palmer J.R., Horton N.J., Fredman L., Wise L.A., Rosenberg L. Racial discrimination and the incidence of hypertension in US black women. Ann. Epidemiol. 2006;16:681-687.

8. Esler M. The 2009 Carl Ludwig Lecture: Pathophysiology of the human sympathetic nervous system in cardiovascular diseases: the transition from mechanisms to medical management. J. Appl. Physiol. 2010;108:227-237.

9. Esler M.D., Krum H., Sobotka P.A., Schlaich M.P., Schmieder R.E., Bohm M. Renal sympathetic denervation in patients with treatmentresistant hypertension (The SymplicityHTN-2 Trial): a randomized controlled trial. Lancet. 2010;376:1903-1909.

10. Folkow B. Psychosocial and central nervous influences in primary hypertension. Circulation. 1987;76(1):110-119.

11. Fredrikson M., Matthews K.A. Cardiovascular responses to behavioral stress and hypertension: a meta-analytic review. Ann. Behav. Med. 1990;12:30-39.

12. Grassi G. Assessment of sympathetic cardiovascular drive in human hypertension: achievements and perspectives. Hypertension. 2009;54:690-697.

13. Guyton A.C. Textbook of Medical Physiology. Philadelphia: W.B. Saunders, 1991.

14. Harrap S.B., Louis W.J., Doyle A.E. Failure of psychosocial stress to induce chronic hypertension in the rat. J. Hypertens. 1984;2:653-662.

15. Hawkley L.C., Masi C.M., Berry J.D., Cacioppo J.T. Loneliness is a unique predictor of age-related differences in systolic blood pressure. Psychol. Aging. 2006;21:152-164.

16. Hawkley L.C., Thisted R.A., Masi C.M., Cacioppo J.T. Loneliness predicts increased blood pressure: 5-year cross-lagged analyses in middle-aged and older adults. Psychol. Aging. 2010;25:132-141.

17. Henry J.P., Stephens P.M., Santisteban G.A. A model of psychosocial hypertension showing reversibility and progression of cardiovascular complications. Circ. Res. 1975;36:156-164.

18. Kahn H.A., Medalie J.H., Neufeld H.N., Riss E., Goldbourt U. The incidence of hypertension and associated factors: the Israel ischemic heart disease study. Am. Heart J. 1972;84:171-182.

19. Kivimeaki M., Head J., Ferrie J.E., Shipley M.J., Steptoe A., Vahtera J., Marmot M.G. Hypertension is not the link between job strain and coronary heart disease in the Whitehall II study. Am. J. Hypertens. 2007;20:1146-1153.

20. Markel A.L. Genetic model of stress-induced arterial hypertension. Izvestiia Akademii nauk SSSR. Seriia biologicheskaia — Proceedings of the USSR Academy of Sciences. Biological Series. 1985;3:466-469.

21. Markel A.L. Behavioral patterns in rats with inherited farterial hypertension. Zhurnal Vysshei Nervnoi Deiatelnosti Imeni I.P. Pavlova — I.P. Pavlov Journal of Higher Nervous Activity. 1986;36(5):956-962.

22. Markel A.L. Development of a new strain of rats with inherited stressinduced arterial hypertension. Genetic Hypertension. Ed. J. Sassard. Colloque INSERM, John Libbey Eurotext Ltd, 1992;218:405-407.

23. Markel A.L., Amstyslavsky S.Ya., Naumenko E.V. The central adrenergic mechanisms of blood pressure regulation in rats with inherited arterial hypertension. Biogenic. Amines. 1987;4(4-6):329-338.

24. Markel A.L., Maslova L.N., Shishkina G.T., Mahanova N.A., Jacobson G.S. Developmental Influences on Blood Pressure Regulation in ISIAH Rats. Eds R. McCarty, D.A. Blizard, R.L. Chevalier. Development of the Hypertensive Phenotype: Basic and Clinical Studies. Amsterdam, Elsevier, 1999.

25. Markel A.L., Galaktionov Yu.K., Efimov V.M. Factor analysis of rat behavior in the open-field test. Zhurnal Vysshei Nervnoi Deiatelnosti Imeni I.P. Pavlova — I.P. Pavlov Journal of Higher Nervous Activity. 1988;38(5):855-863

26. Markel A.L., Redina O.E., Gilinsky M .A., Dymshits G.M., Kalashniva E.V., Khvrostova Yu.V., Fedoseeva L.A., Jacobson G.S. Neurendocrine profiling in inherited stress-induced arterial rat strain with stress-sensitive arterial hypertension. J.Endocrinol. 2007;195:439-450.

27. Markel A.L., Shishkina G.T. Genetic correlation between the arterial pressure response during emotional stress and the alpha1-adrenoreceptor concentration in brain regions. Genetika — Genetics (Moscow). 1992;28(11):130-133.

28. Martins J.M., do Vale S., Martins A.F. Mild adrenal steroidogenic defects and ACTH-dependent aldosterone secretion in high blood pressure: preliminary evidence. Intern. J. Endocrinol. 2014; Article ID 295724, 8 pages. DOI: 10.1155/2014/295724

29. Maslova L.N., Shishkina G.T., Bulygina V.V., Markel A.L., Naumenko E.V. Brain catecholamines and the hypothalamo-hypophyseal-adrenocortical system in hereditary arterial hypertension. Fiziologicheskii Zhurnal Imeni I.M. Sechenova — Russian Journal of Physiology. 1996;82(4):30-37

30. Maslova L.N., Shishkina G.T., Bulygina V.V., Markel A.L., Naumenko E.V. Brain catecholamines and the hypothalamo-hypophysealadrenocortical system in inherited arterial hypertension. Neurosci. Behav. Physiol. 1998;28(1):38-44.

31. Meshkov I.O., Alekhina T.A., Moreva T.A., Markel A.L Behavioral . characterictics of ISIAH rat strain. Zhurnal Vysshei Nervnoi Deiatelnosti Imeni I.P. Pavlova — I.P. Pavlov Journal of Higher Nervous — I.P. Pavlov Journal of Higher Nervous Activity. 2012;62(2):233-242.

32. Moraitis A., Stratakis C. Adrenocortical Causes of Hypertension. SAGE-Hindawi Access to Res. Int. J. Hypertens. 2011; Article ID 624691, 10 pages. DOI: 10.4061/2011/624691

33. Nalivaiko E. Frontiers in research review: stress and hypertension animal models of psychogenic cardiovascular disorders: what we can learn from them and what we cannot. Clin. Expr. Pharmacol. Physiol. 2011;38:115-125.

34. Naumenko E.V., Maslova L.N., Gordienko N.I., Amstyslavski S.Y., Dygalo N.N., Markel A.L. Persistent hypotensive effect of l-DOPA given early during development to rats with inherited stress-induced arterial hypertension. Devel. Brain Res. 1989;46:205-212.

35. Naumenko E.V., Maslova L.N., Markel A.L. Correction of arterial blood pressure in adult rats with inherited stress-induced arterial hypertension by enhancement of catecholamine metabolism in early postnatal period. Endocrinol. Experim. 1990;24:241-248.

36. Pickering T., James G., Boddie C., Harshfield G., Blank S., Laragh J. How common is white coat hypertension? JAMA. 1988;259(2):225-228. DOI: 10.1001/jama.259.2.225

37. Roger V.L., Go A.S., Lloyd-Jones D.M., Benjamin E.J., Berry J.D., Borden W.B., Bravata D.M., Dai S., Ford E.S., Fox C.S., Fullerton H.J., Gillespie C., Hailpern S.M., Heit J.A., Howard V.J., Kissela B.M., Kittner S.J., Lackland D.T., Lichtman J.H., Lisabeth L.D., Makuc D.M., Marcus G.M., Marelli A., Matchar D.B., Moy C.S., Mozaffarian D., Mussolino M.E., Nichol G., Paynter N.P., Soliman E.Z., Sorlie P.D., Sotoodehnia N., Turan T.N., Virani S.S., Wong N.D., Woo D., Turner M.B. Heart disease and stroke statistics: 2012 update: a report from the American Heart Association. Circulation. 2012;125:e2-e220.

38. Shankar A., McMunn A., Banks J., Steptoe A. Loneliness, social isolation, and behavioral and biological health indicators in older adults. Health Psychol. 2011;30:377-385.

39. Sparrenberger F., Cichelero F.T., Ascoli A.M., Fonseca F.P., Weiss G., Berwanger O., Fuchs S.C., Moreira L.B., Fuchs F.D. Does psychosocial stress cause hypertension? A systematic review of observational studies. J. Hum. Hypertens. 2009;23:12-19.

40. Trudel X., Brisson C., Milot A. Job strain and masked hypertension. Psychosom. Med. 2010;72:786-793.

41. Waddington C.H. Genetic assimilation. Adv. Genet. 1961;10:257-290.

This entry was posted in Tom 19-4. Bookmark the permalink.