Is Hypertension a Bone Marrow Disease?
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Article, see p 1353
Hypertension affects 30% of the population and 70% of elderly adults. Despite its frequency and decades of research, the etiology of most cases of adult hypertension remains undefined. Perturbations of the kidney, the vasculature, and the central nervous system have all been implicated in the pathogenesis of hypertension. As examples, in most cases of adult hypertension, systemic vascular resistance is elevated and vasodilators lower blood pressure, supporting a vascular etiology. Alternatively, renal cross-transplantation studies have shown that hypertension follows the kidney, and in most cases of experimental hypertension, pressure natriuresis is impaired. Likewise, most single-gene mutations that cause hypertension affect sodium transport in the distal nephron. In keeping with a renal etiology, diuretics and sodium restriction are effective in lowering blood pressure. There is ample evidence to suggest a central-neural cause of hypertension. Sympathetic outflow is almost uniformly increased in experimental models of hypertension and in humans with this disease, and renal denervation has been variably reported to reduce blood pressure. Adrenergic receptor antagonists are commonly used to treat hypertension, further supporting a neural etiology.
Is there a unifying mechanism that underlies abnormalities of the brain, kidneys, and the vasculature in hypertension? Accumulating evidence shows that immune cells infiltrate these organs in response to hypertensive stimuli, causing their dysfunction and leading to elevated blood pressure and subsequent end-organ damage. Both innate and adaptive immune cells play a key role in this process. Monocyte/macrophages are increased in the kidney and vasculature of animal models of experimental hypertension and in humans with hypertension. Wenzel et al1 showed that deletion of monocytes/macrophages completely eliminates angiotensin II-induced hypertension and markedly improves vascular function. Monocytes have several fates on tissue entry. One is to become inflammatory macrophages that can generate reactive oxygen species, release cytokines, and produce matrix metalloproteinases. A …