L-arginine attenuates ketamine-induced increase in renal sympathetic nerve activity.
BACKGROUND
It has been reported that ketamine produces sympathoexcitation by directly stimulating the central nervous system. It also has been shown that nitric oxide (NO) may play a role in signal transduction of the nervous system. Therefore, we hypothesized that the sympathoexcitation of ketamine may be linked to central NO formation. To test this hypothesis, we examined the effects of L-arginine, a substrate of NO formation, on renal sympathetic nerve activity (RSNA) during ketamine anesthesia.


METHODS
Using 45 rabbits given basal anesthesia with alpha-chloralose, we measured changes in heart rate, mean arterial pressure, and RSNA in response to intravenous ketamine (1 mg/kg) and investigated the effect of intravenous L-arginine and D-arginine (bolus 30 mg/kg followed by continuous 30 mg.kg-1.min-1). The animals were divided into intact, sinoaortic- and vagal-deafferented, and spinal cord-transected groups.


RESULTS
Ketamine caused significant increases in RSNA (172 +/- 16%), heart rate (12 +/- 2 beats/min), and mean arterial pressure (8 +/- 1 mmHg) in the intact rabbits. Ketamine also increased RSNA in sinoaortic- and vagal-deafferented rabbits, but not in spinal cord-transected rabbits. L-Arginine attenuated the ketamine-induced increase in RSNA in intact and deafferented rabbits, whereas D-arginine had no effect on RSNA. In addition, NG-nitro-L-arginine methyl ester, a NO synthase inhibitor, increased RSNA and the increase was attenuated by L-arginine.


CONCLUSIONS
Ketamine may act centrally to increase sympathetic outflow, and the sympathoexcitation may be attenuated by increasing NO formation with L-arginine in the central nervous system.
Okamoto
H
H
Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Hoka
S
S
Kawasaki
T
T
Okuyama
T
T
Takahashi
S
S
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D007649:Ketamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000294:innervation*; D019331:NG-Nitroarginine Methyl Ester; D011817:Rabbits; D013116:Spinal Cord / Q000502:physiology / Q000601:surgery; D013237:Stereoisomerism; D013564:Sympathetic Nervous System / Q000187:drug effects*
D007649:Ketamine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester