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