Kp. Patel et al., BLUNTING OF RENAL EXCRETORY RESPONSES TO ACUTE VOLUME EXPANSION BY NICOTINE - ROLE OF RENAL NERVES, The Journal of pharmacology and experimental therapeutics, 274(3), 1995, pp. 1174-1181
During smoking, an activated sympathetic nervous system can produce a
variety of adverse effects on the cardiovascular system. There is evid
ence of increased renal nerve activation during smoking; however, whet
her the increased renal nerve activation in smokers translates into so
dium retention by the kidney remains to be determined. In the present
study, we examined the effect of nicotine on the renal nerve-mediated
handling of sodium by the kidney during an acute volume expansion (VE)
with isotonic saline (0.25% of body weight per minute for 30 or 40 mi
n). Urine flow and sodium excretion from intact and denervated kidneys
were measured before and during an acute graded VE in anaesthetized c
ontrol and nicotine-treated rats (2 mu g/kg/min for 10 min before and
20 min during VE, respectively). In rats treated with nicotine, VE pro
duced a significantly blunted diuresis (33% of control by 7.5% VE) and
natriuresis (36% of control by 7.5% VE) from the intact kidneys compa
red with control rats. Glomerular filtration rate was not significantl
y different between the two groups, indicating that hemodynamic change
s per se were not responsible for the altered volume reflex in rats in
fused with nicotine. However, renal denervation abolished the differen
ce between the control and nicotine-treated rats in diuresis and natri
uresis in response to VE. In addition, the decrease in renal nerve act
ivity (renal sympathoinhibition) in response to acute VE was significa
ntly blunted (53% of control by 5% VE) in rats treated with nicotine c
ompared with the control rats. Because smoking leads to chronic elevat
ion of nicotine, we simulated a chronic elevation of nicotine by admin
istering nicotine (2 mg/kg/day) for 1 week. Acute graded VE also produ
ced a significantly blunted renal sympathoinhibition (30% of control b
y 10% VE), diuresis (48% of control by 7.5% VE) and natriuresis (54% o
f control by 7.5% VE) in rats chronically treated with nicotine compar
ed with control rats. These results suggest that the impaired ability
to excrete an acute isotonic saline load in the presence of nicotine i
s in part dependent on basal efferent renal sympathetic nerve activity
that fails to suppress normally in response to the isotonic saline lo
ad.