Sympathetic Hyperactivity in Chronic Renal Failure

Abstract

Abstract. Sympathetic hyperactivity plays an important and distinct role in hypertension associated with chronic renal failure (CRF). Renal ischemia, elevated angiotensin II, and suppressed brain nitric oxide (NO) all stimulate sympathetic activity. Evidence is accumulating for a role of sympathetic hyperactivity in renal and cardiac damage in patients with CRF. Decreased NO availability and increased oxidative stress, characteristic in CRF patients, seem to sensitize target organs for damaging actions of sympathetic hyperactivity. Fortunately, sympatholytic agents can slow down progression of renal and cardiac dysfunction. Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists suppress sympathetic activity, but complete elimination of the effect of sympathetic hyperactivity can be obtained only with specific adrenergic blockers. However, this important therapeutic option is grossly neglected, painfully illustrated by the unwillingness to treat CRF patients with ␤-blockers, even if they have had a myocardial infarction. After discussion of mechanisms and effects of the sympathetic hyperactivity, a case is made for increased application of specific adrenergic blockers in patients with CRF.Hypertension remains an important issue in patients with chronic renal failure (CRF). It plays a key role in progression of renal failure and forms the basis for the cardiovascular complications and mortality. Although this point is widely recognized, BP control in patients with CRF, whether in an early or advanced stage or when on dialysis, is often poor (1, 2).Hypervolemia and activated renin angiotensin system (RAS) have long been acknowledged as major determinants of hypertension in CRF, and in most patients, both need to be controlled to normalize BP. Besides, it has been shown in several trials that the renoprotective effect of RAS suppression extends beyond BP lowering only. This applies particularly to patients with diabetic (3-6) or nondiabetic (3, 5, 7) glomerulopathy.It has also become clear that many other factors cause renal hypertension. These include elevated levels of endothelin, sympathetic activity, and oxidant stress and reduced levels of NO and medullary vasodilating factors (8 -10). As is the case for angiotensin II, many of these factors probably damage the kidney and the cardiovascular system independent of their hypertensive effect. However, as long as their pathogenic role has not been proved in large clinical trials, it is understandable that these factors are still regarded as foot-soldiers compared with the well-accepted nobility of volume and RAS-understandable, but probably not right. Already several Cinderellas have been identified that relate CRF to cardiovascular disease, i.e., the underestimated role of renal dysfunction in cardiovascular risk profile (11) and of cardiac systolic dysfunction in dialysis patients (12). We can do without one more. In this review, we highlight the pathogenesis of sympathetic hyperactivity in CRF and the evidence for its role in organ damage...

The Challenge of Sudden Death in Dialysis Patients

“…If the results are confirmed, then one would anticipate that catecholamine concentrations increase in parallel with the decrease in the renal production of renalase. The impact of sympathetic overactivity may be amplified by the fact that the counterbalancing effect of the parasympathetic system is attenuated in renal disease; furthermore, target organs are sensitized to catecholamine action by diminished availability of nitric oxide (53).…”

“…Sympathetic overactivity may certainly be a causal factor in the genesis of sudden death, but prospective evidence is lacking. The risk may be further increased by autonomic polyneuropathy and patchy denervation of sympathetic fibers with consequent catecholamine receptor upregulation in the remnant fibers and by lesser bioavailability of nitric oxide, which antagonizes many effects of catecholamines (53).…”

Metalloproteinases: key and common mediators of multiple GPCRs and candidate therapeutic targets in models of hypertensive cardiac disease

“…Similar to diabetes [5] and obesity [7], chronic stress (e.g. due to job strain, social environment or emotional distress) [6,[8][9][10][11][12] and genetic predisposition [2,13] can cause various degrees of hypertension and cardiac disease. The major mechanism of disease by chronic stress is sympathetic nervous system activation, which results in high systemic or local (on target organs) production of stress hormones (e.g.…”

Chromogranin A Polymorphisms Are Associated With Hypertensive Renal Disease

“…The findings of this study can be viewed in the context of a growing literature implicating sympathetic nervous system (SNS) hyperactivity as a mechanism of renal injury and disease progression. 50,56 Sympathetic hyperactivity has been well described in patients with chronic renal failure 57 and may represent both a consequence of the disease 57 and a factor in its origin and progression. 56 Blacks are the population at highest risk of developing hypertensive ESRD, 26,29 -34 and this same population may display exaggerated autonomic responses to environmental stressors.…”

“…50,56 Sympathetic hyperactivity has been well described in patients with chronic renal failure 57 and may represent both a consequence of the disease 57 and a factor in its origin and progression. 56 Blacks are the population at highest risk of developing hypertensive ESRD, 26,29 -34 and this same population may display exaggerated autonomic responses to environmental stressors. 46 -49 Johnson et al 58 suggested a model in which elevated sympathoadrenal tone may be one starting point for a chain of events leading to renal parenchymal damage.…”