Review article
Target organ involvement in hypertension: a realistic promise of prevention and reversal

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Hypertensive heart disease

A constellation of structural, functional, and endothelial pathophysiologic mechanisms that effect coronary hemodynamics and ventricular function explain the clinical outcomes caused by hypertensive heart disease. Structural alterations associated with hypertension that directly impact on coronary blood flow include vascular compression by the hypertrophied LV, increased wall thickening of the coronary arterioles that increase the wall:lumen ratio, and luminal obstruction from atherosclerotic

Effects of hypertension on the heart

Until recently, the only major cardiac involvement in hypertension that was considered in any depth clinically was LVH [29]. Indeed, LVH is considered an extremely important epidemiologic risk factor that underlies CHD, even more than the height of arterial pressure [9], [30], [31]. The precise mechanisms associated with this increased risk now seem to be appearing [9], [28]; but whether the risk of LVH per se is diminished by the antihypertensive therapy that reduces ventricular mass

Effects of aging on hypertension

Perhaps the most striking alterations involving left and right ventricular hemodynamics changes with age were demonstrated in the author's experimental SHR studies involving 20- to 65-week-old SHRs with ischemia of the hypertrophied LV and the nonhypertrophied right ventricle. Moreover, it was of particular interest that the ischemic changes of both ventricles also occurred in normotensive age- and gender-matched WKY rats [33]. Specifically, in that study, the author demonstrated reduced left

Apoptosis

Still more recently, a relatively new pathophysiologic phenomenon has been related to the problem of hypertensive heart disease: the alteration of programmed cellular death or apoptosis of the ventricle [26], [27], [28]. Programmed cellular death is in striking contrast to the cellular death achieved by sudden ischemia, such as that produced by acute vascular occlusion with myocardial infarction. The process of apoptosis seems to be initiated when a locally produced agent (eg, angiotensin)

Therapeutic intervention

Adverse changes in coronary hemodynamics have been related to progressive hypertensive disease and aging, and are manifested by normal or reduced resting blood flow and increased vascular resistance and impaired coronary flow reserve [14], [15], [16], [17], [18], [19], [33]. In addition to LVH, important other structural and functional coronary vascular changes occur in hypertension. These include a thickened arteriolar wall of hypertensive vascular disease clearly manifested in the coronary

Endothelial dysfunction in hypertension

Endothelial dysfunction complicates hypertension-related hemodynamic changes [19], [20], [21], [22], [23], [24], [25]. This alteration is distinctly different from the classical abnormality of hypertensive arteriolar disease. It also occurs in a number of other clinical conditions (eg, aging, menopause, tobacco smoking, hypertension, diabetes mellitus, obesity, atherosclerosis, hyperlipidemia, hyperhomocysteinemia, and cardiac failure). Moreover, a number of differing but disease-specific

Renal involvement in hypertension

End-stage renal disease also continues to increase in patients with essential hypertension, particularly in black patients and in patients with diabetes mellitus. Because hypertension is exceedingly common in diabetes, hypertension should be considered as the major contributor to the development of ESRD [50].

The renal and glomerular hemodynamic changes characteristic of ESRD include afferent arteriolar constriction that diminishes total renal blood flow and blood flow to the glomerulus and

Summary

The major message from this discussion is that the end points from hypertensive disease (stroke, CHD, and hypertensive emergencies) are now preventable. Cardiac failure and ESRD, however, two exceedingly common end points from long-standing hypertension, remain as major disabilities and causes of death. The former is the most common cause of hospitalization in industrialized societies; hypertension and diabetes mellitus are the most common causes of the latter. The mechanisms of risk of these

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