BLUNTING OF RENAL EXCRETORY RESPONSES TO ACUTE VOLUME EXPANSION BY NICOTINE - ROLE OF RENAL NERVES

Citation
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
Citations number
26
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00223565
Volume
274
Issue
3
Year of publication
1995
Pages
1174 - 1181
Database
ISI
SICI code
0022-3565(1995)274:3<1174:BORERT>2.0.ZU;2-5
Abstract
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.