Book Review

Essential Hypertension and Its Causes: Neural and Non-Neural Mechanisms

N Engl J Med 2008; 358:1763-1764April 17, 2008

Article

Essential Hypertension and Its Causes: Neural and Non-Neural Mechanisms
By Paul Korner. 690 pp., illustrated. New York, Oxford University Press, 2007. $98.50. ISBN: 978-0-19-509483-1

Many people believe that the cause of essential hypertension remains unknown. In Essential Hypertension and Its Causes, Paul Korner aims to identify the pathogenesis of essential hypertension by bringing together a considerable amount of knowledge in a coherent and clinically relevant manner. He makes a strong argument that instead of originating from the kidneys, essential hypertension is triggered primarily through the nervous system and is later reinforced by nonneural factors.

The book has three interwoven objectives: to define the main initiating causes of essential hypertension, to elucidate the mechanisms by which blood pressure is raised, and to assess the major factors that contribute to the progressive elevation of blood pressure over time. Korner begins with a review of the history and clinical features of essential hypertension and follows it with an examination of the nature of the circulatory system, differentiating between the model of the linear control system that has fixed regulatory parameters and set points and the more innovative, nonlinear system of adaptive control that has parameters that alter automatically. This idea of the nonlinear system is the crux of Korner's theory that although the inheritance of essential hypertension is polygenic, environmental factors play a pivotal role in the development of hypertension. Through animal models that use borderline hypertensive rats (a hybrid of the spontaneously hypertensive rat and Wistar Kyoto rat strains), he attempts to show that although hypertension is initiated through hypothalamic cardiovascular neurons, stressors such as a diet high in salt, psychological stress, and obesity serve to sensitize and strengthen the synaptic transmission of the dopaminergic neurons, which makes the rats prone to the development of sustained hypertension. It is precisely this hypothalamic defense response, evoked by stress, that is responsible for the characteristic functional and structural changes in the vasculature that inevitably cause deterioration of the function of vital organs.

Korner's hypothesis is unique in that it emphasizes the role of the central nervous system and adaptive nonlinear systems over Arthur Guyton and Lewis Dahl's famous dictum, “blood pressure travels with the kidney.” This hypothesis leads to Korner's declaration that the kidney is a “long-term victim of nonrenal influences” and “is not the initial source of hypertension.” Korner supports this claim through his analysis of the mechanisms of hypertension in the Goldblatt kidney (renal artery stenosis) and the Page kidney (renal cellophane wrap), and in experiments with low renal mass that demonstrate that the decrease in the number of nephrons is a consequence of neurally mediated vasoconstriction. Moreover, Korner underscores the importance of nonpharmacologic interventions (e.g., regular exercise and dietary modifications) not only in the treatment of essential hypertension, but also in its prevention. He raises the excellent point that although essential hypertension is activated via neural autonomic mechanisms, nonneural factors make an even greater contribution to the rise in blood pressure.

Although the author presents his case in a systematic and engaging manner, at times the reader may feel overwhelmed by the data shown in the complicated figures and graphs. Furthermore, this book will likely be an invaluable resource for hypertension researchers and neuroscientists, rather than for clinicians, since the multitude of details on the pathophysiology of essential hypertension may not necessarily alter patient care and current management of hypertension. After all, one must realize that the present understanding of underlying mechanisms is based largely on the analysis of animal models — not human models. Overall, Essential Hypertension and Its Causes offers a fresh perspective on the putative causes of hypertension. This perspective may shift the focus of some research to the further illumination of neural mechanisms in the hope of finding new therapeutic measures — or perhaps a way to prevent essential hypertension altogether.

Susan Phung, M.D.
Franz H. Messerli, M.D.
St. Luke's Roosevelt Hospital Center, New York, NY 10019
sp297@columbia.edu