Abstract
While many studies have attempted to produce hypertension through the use of various environmental Stressors, few have succeeded in producing chronic elevations in blood pressure beyond levels considered to be borderline hypertensive (140–160 mm Hg systolic). The problem with most studies stems from the use of genetically normotensive animals and the selection of Stressors to which animals readily adapt. A new approach is suggested, which recognizes the role of genetics in human essential hypertension. Animals with one hypertensive parent do not develop spontaneous hypertension but show a more sensitive cardiovascular response to environmental Stressors than animals with normotensive parents. Preliminary studies revealed that animals with a mixed genetic history of hypertension develop spontaneous borderline hypertension. When subjected to shock-shock conflict, these borderline hypertensive rats (BHR) developed permanent hypertension that failed to abate even after a ten-week, shock-free recovery period. The hypertension was accompanied by elevated heart weight to body weight ratios and by significant cardiac pathology. Subsequent work has demonstrated that these animals also become hypertensive when fed a high-sodium diet. Finally, in a series of exercise studies, we found that BHRs subjected to a shock stressor were protected against stress-induced hypertension if they exercised daily. The potential of this model for studies of the mechanisms by which environmental variables produce permanent hypertension is discussed.
Similar content being viewed by others
References
Aceto, M. D. G., Kinnard, W. T., and Buckley, J. P. Effects of compounds on blood pressure and behavioral responses of rats chronically subjected to an avoidance-escape situation.Archives Internationales de Pharmacodynamie et de Therapie, 1963,144, 214–225.
Alexander, N. Psychosocial hypertension in members of a Wistar rat colony.Proceedings of the Society for Experimental Biology and Medicine, 1974,146, 163–169.
Anderson, D. E., and Tosheff, J. G. Cardiac output and total peripheral resistance changes during preavoidance periods in the dog.Journal of Applied Physiology, 1973,34, 650–654.
Brady, J. V., Findley, J. D., and Harris, A. Experimental psychopathology of emotion. In H. D. Kimmel (Ed.),Experimental Psychopathology. New York: Academic Press, 1971.
Chen, A. K., and Evonuk, E. Changes in plasma catecholamine and corticosterone levels after muscular exercise.Journal of Applied Physiology, 1971,30, 205–207.
Cox, R. H., Hubbard, J. W., Lawler, J. E., Sanders, B. J., and Mitchell, V. P. Exercise training attenuates stress-induced hypertension in the rat.Hypertension, in press.
Dykman, R. A., and Gantt, H. Experimental psychogenic hypertension: Blood pressure changes conditioned to painful stimuli (schizokinesis).Bulletin Johns Hopkins Hospital, 1960,107, 72–89.
Folkow, B. Physiological aspects of primary hypertension.Physiological Reviews, 1982,62, 347–504.
Forsyth, R. P. Blood pressure and avoidance conditioning: A study of 15-day trials in the rhesus monkey.Psychosomatic Medicine, 1968,30, 125–135.
Forsyth, R. P. Blood pressure responses to long-term avoidance schedules in the restrained rhesus monkey.Psychosomatic Medicine, 1969,31, 300–309.
Friedman, R. Experimental psychogenic hypertension. In D. Wheatley (Ed.),Stress and the Heart (2nd edition). New York: Raven Press, 1981.
Friedman, R., and Dahl, L. K. The effect of chronic conflict on the blood pressure of rats with a genetic susceptibility to experimental hypertension.Psychosomatic Medicine, 1975,37, 402–416.
Friedman, R., and Iwai, J. Genetic predisposition and stress-induced hypertension.Science, 1976,193, 161–162.
Galosy, R. A., and Gaebelein, C. J. Cardiovascular adaptation to environmental stress: Its role in the development of hypertension, responsible mechanisms and hypotheses.Biobehavioral Reviews, 1977,1, 165–175.
Hallback, M. Consequence of social isolation on blood pressure, cardiovascular reactivity and design in spontaneously hypertensive rats.Acta Physiologica Scandinavica, 1975,93, 455–465.
Hallback, M. Interaction between central neurogenic mechanisms and changes in cardiovascular design in primary hypertension.Acta Physiologica Scandinavica, 1975,Suppl. 424, 1–59.
Harpur, R. P. The rat as a model of physical fitness studies.Comparative Biochemistry and Physiology, 1980,66, 553–574.
Henry, J. P., Stephens, P. M., and Santisteban, G. A. A model of psychosocial hypertension showing reversibility and progression of cardiovascular complications.Circulation Research, 1975,36, 156–164.
Herd, J. A., Morse, W. H., Kelleher, R. T., and Jones, L. G. Arterial hypertension in the squirrel monkey during behavioral experiments.American Journal of Physiology, 1969,217, 24–29.
Holoszy, J. O. Exercise, health and aging: A need for more information.Medicine and Science in Sports and Exercise, 1983,15, 1–5.
Hudak, W. J., and Buckley, J. P. Production of hypertensive rats by experimental stress.Journal of the Pharmaceutical Sciences, 1961,50, 263–264.
Lais, L. T., Bhatnagar, R. A., and Brody, M. J. Inhibition by dark adaptation of the progress of hypertension in the spontaneously hypertensive rat (SHR).Circulation Research, 1974,34-35(Suppl. I), 155–160.
Lawler, J. E., Obrist, P. A., and Lawler, K. A. Cardiovascular function during pre-avoidance, avoidance, and post-avoidance in dogs.Psychophysiology, 1975,12, 4–12.
Lawler, J. E., Barker, G. F., Hubbard, J. W., and Allen, M. T. The effects of conflict on tonic levels of blood pressure in the genetically borderline hypertensive rat.Psychophysiology, 1980,17, 363–370.
Lawler, J. E., Barker, G. F., Hubbard, J. W., and Schaub, R. G. The effects of stress on blood pressure and cardiac pathology in rats with borderline hypertension.Hypertension, 1981,3, 496–505.
Lawler, J. E., Barker, G. F., Hubbard, J. W., Cox, R. H., and Randall, G. W. Blood pressure and plasma renin activity responses to chronic stress in the borderline hypertensive rat.Physiology and Behavior, 1984,32, 101–105.
Perhach, J. L., Ferguson, H. C., and McKinney, G. R. Evaluation of antihypertensive agents in the stressinduced hypertensive rat.Life Sciences, 1975,16, 1731–1736.
Scheur, J., and Tipton, C. M. Cardiovascular adaptations to training.Annual Review of Physiology, 1977,39, 221–251.
Shapiro, A. P., and Melhado, J. Observations on blood pressure and other physiologic and biochemical mechanisms in rats with behavioral disturbances.Journal of Psychosomatic Medicine, 1958,20, 303–313.
Smookler, H. H., and Buckley, J. P. Relationships between brain catecholamine synthesis, pituitary adrenal function and the production of hypertension during prolonged exposure to environmental stress.International Journal of Neuropharmacology, 1969,8, 33–41.
Turkkan, J. S., Brady, J. V., and Harris, A. H. Animal studies of stressful interactions: A behavioralphysiological overview. In L. Goldberger and S. Breznitz (Eds.),Handbook of Stress: Theoretical and Clinical Aspects. New York: Free Press, 1982.
Vander, A. J., Henry, J. P., Stephens, P. M., Kay, L. L., and Mouw, D. R. Plasma renin activity in psychosocial hypertension of CBA mice.Circulation Research, 1978,42, 496–502.
Yamori, Y., Matsumoto, M., Yamabe, H., and Okamoto, K. Augmentation of spontaneous hypertension by chronic stress in rats.Japanese Circulation Journal, 1969,33, 399–409.
Author information
Authors and Affiliations
Additional information
Research Investigator, American Heart Association, Tennessee Affiliate (7/82-6/84). Supported by Research Career Development Award HL-01395 (7/84-6/ 89).
Supported by postdoctoral fellowship HL-06036 from the USPHS.
Research supported by grants from the NIH (HL-19680) and the American Heart Association, Tennessee Affiliate to JEL, and by a Biomedical Sciences Support Grant (7088) to the University of Tennessee, Knoxville.
This article is based on an invited presentation given at the Annual Meeting of the Pavlovian Society, November 16–18, 1983.
Rights and permissions
About this article
Cite this article
Lawler, J.E., Cox, R.H. The borderline hypertensive rat (BHR): A new model for the study of environmental factors in the development of hypertension. Pav. J. Biol. Sci. 20, 101–115 (1985). https://doi.org/10.1007/BF03003593
Issue Date:
DOI: https://doi.org/10.1007/BF03003593