Abstract
Hypertension is a major health concern in the developed world, and its prevalence increases with advancing age. The impact of hypertension on the function of the renal and cardiovascular systems is well studied; however, its influence on the brain regions important for cognition has garnered less attention. We utilized the Cyp1a1‐Ren2 xenobiotic‐inducible transgenic rat model to mimic both the age of onset and rate of induction of hypertension observed in humans. Male, 15‐month‐old transgenic rats were fed 0.15% indole‐3‐carbinol (I3C) chow to slowly induce renin‐dependent hypertension over a 6‐week period. Systolic blood pressure significantly increased, eventually reaching 200 mmHg by the end of the study period. In contrast, transgenic rats fed a control diet without I3C did not show significant changes in blood pressure (145 mmHg at the end of study). Hypertension was associated with cardiac, aortic, and renal hypertrophy as well as increased collagen deposition in the left ventricle and kidney of the I3C‐treated rats. Additionally, rats with hypertension showed reduced savings from prior spatial memory training when tested on the hippocampus‐dependent Morris swim task. Motor and sensory functions were found to be unaffected by induction of hypertension. Taken together, these data indicate a profound effect of hypertension not only on the cardiovascular‐renal axis but also on brain systems critically important for learning and memory. Future use of this model and approach may empower a more accurate investigation of the influence of aging on the systems responsible for cardiovascular, renal, and neurological health.
Highlights
Hypertension is the leading risk factor for cardiovascular disease affecting 40% of middle-aged adults 45–64 years and 70% of adults over the age of 65 in the United States (Gillespie and Hurvitz 2013). Wilkie and Eisdorfer (1971) first reported that the degree of hypertension in adults in their 60s was associated with significant intellectual a 2019 The Authors
Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society
The experiments in this study examined the cardiovascular, renal, and neurological effects of hypertension induction in middle-aged rats
Summary
Hypertension is the leading risk factor for cardiovascular disease affecting 40% of middle-aged adults 45–64 years and 70% of adults over the age of 65 in the United States (Gillespie and Hurvitz 2013). Wilkie and Eisdorfer (1971) first reported that the degree of hypertension in adults in their 60s was associated with significant intellectual a 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. Hypertension Impairs Memory in Middle-Aged rats decline over a 10-year period. This general finding has been replicated and extended most recently in results from the Women’s Health Initiative Memory Study, in which it was found that postmenopausal women with hypertension are at higher risk for cognitive decline (Haring et al 2013). The exact relationship between hypertension and cognitive decline, remains to be discovered
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