Blankestijn PJ, Ligtenberg G, Dijkhorst LT, Oey PL, Wieneke G, Koomans HA
Direct evidence for suppression of sympathetic activity in chronic renal failure by enalapril
Am Soc Nephrol
J Am Soc Nephrol (abstract) (Sep) 7:1546 1996

It is known that sympathetic nerve activity plays an important role in the maintenance of hypertension in patients with chronic renal failure and ESRD. ACE inhibitors can indirectly reduce sympathetic activity by decreasing angiotensin II (AII) stimulation of preganglionic sympathetic nerve endings, a known target tissue for AII. The authors of this study tested the hypothesis that enalapril and ACE inhibitor could reduce sympathetic nerve activity in patients with non-diabetic chronic renal failure (Ccr 14-63 ml/min). Accordingly they performed blood pressure, heart rate, barorecptor activity, and microneurography measurements of peroneal nerve sympathetic afferents in patients (N=8) and normal controls (N=7).

The latter technique is a well established experimental method for directly measuring sympathetic activity in humans. Sympathetic activity can be easily separated from other neuron activity using this technique and effects of stimulants or suppressants of sympathetic activity can be reliably measured and monitored.

They found that blood pressure and sympathetic nerve activity were both increased in the patients with CRF. Importantly, acute enalaprilat and chronic enalapril administration reduced blood pressure and sympathetic nerve activity in patients with chronic renal failure. In contrast acute nitroprusside administration in the same patients produced a similar reduction in blood pressure but was accompanied by increased sympathetic activity. The authors conclude that this is the first study to show a direct effect of enalapril on sympathetic nerve activity in patients with chronic renal failure. They speculate that this effect of enalapril may help to lower blood pressure and preserve renal function as well as reduce the adverse consequences of sympathetic overactivity on the CV system.

Comment: This is a carefully done study on the surface. It is noteworthy in that few studies have used this technique to probe the effects of any drug that interrupts the renin-angiotensin system (RAS) in patients with renal disease. It is also important to note that this study was not done in diabetics because it is difficult if not impossible to obtain an evaluable nerve recording in such patients presumably because of diabetic neuropathy. The fact that ACE inhibitors have the effect postulated in this patient population is not a surprise but it is a new finding. It would be interesting to know whether the same effect occurred with clonidine as another control situation and an angiotensin II receptor blocker as an additional RAS blocker. (Robert D. Toto, M.D., University of Texas Southwestern Medical Center)

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Am Soc Nephrol
H: Pathophysiology : Sympathetic nervous system
CRF by organ system : Cardiovascular/Hypertension