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Pathways involved in the transition from hypertension to hypertrophy to heart failure. Treatment strategies

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Abstract

The renin-angiotensin-aldosterone system (RAAS) is critical in regulating systemic blood pressure, water and electrolyte balance, and pituitary gland hormones. These physiologies appear to be primarily mediated by the angiotensin II/AT1 receptor subtype system. Overstimulation of this system can predispose cardiovascular disease (CVD) characterized by excessive vasoconstriction, fibrosis, and cardiac remodeling. If untreated, the patient typically displays a continuum of pathophysiologic conditions progressing from atherosclerosis to left ventricle hypertrophy (LVH), coronary thrombosis, myocardial infarcts, with heart failure as an endpoint. Intervention with antihypertensive therapy is necessary to inhibit this progression. RAAS blocking drugs appear to be the most effective approach. Diastolic heart failure patients benefit from treatment with angiotensin converting enzyme (ACE) inhibitors and angiotensin AT1 receptor blockers (ARBs). Elderly CVD patients evidence age-related changes in body composition that alter the distribution and half-life of medications, thus presenting special challenges to treatment. The presence of comorbidities such as diabetes, renal dysfunction, liver insufficiency further complicates any therapeutic strategy. In addition, noncompliance because of cognitive impairment, depression, confusion due to the complexity of dose regimens, and lack of an appropriate social support system can disrupt positive outcome. The present review discusses the roles of an overactive RAAS and sympathetic nervous system as primary contributors to CVD. In addition, treatment strategies are discussed, focusing on middle aged and elderly hypertensive and heart failure patients.

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Acknowledgments

The research from our laboratory presented in this review was supported by NIH grant RO1-HL64245-03, NSF grant IBN-0091337, and the Edward E. and Lucille I. Lainge Endowment for Alzheimer’s Research. We thank Mrs. Ruth Day for secretarial assistance provided during the course of writing this manuscript.

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  1. Department of Psychology, Washington State University, P.O. Box 644820, Pullman, WA, 99164-4820, USA

    John W. Wright & Joseph W. Harding

  2. Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA, 99164-4820, USA

    John W. Wright & Joseph W. Harding

  3. Programs in Neuroscience and Biotechnology, Washington State University, Pullman, WA, 99164-4820, USA

    John W. Wright & Joseph W. Harding

  4. Department of Medical Science of Proteases, Graduate School of Medicine, Nagoya University, Nagoya, Japan

    Shigehiko Mizutani

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Wright, J.W., Mizutani, S. & Harding, J.W. Pathways involved in the transition from hypertension to hypertrophy to heart failure. Treatment strategies. Heart Fail Rev 13, 367–375 (2008). https://doi.org/10.1007/s10741-007-9060-z

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