L-ARGININE ATTENUATES KETAMINE-INDUCED INCREASE IN RENAL SYMPATHETIC-NERVE ACTIVITY

Background: It has been reported that ketamine produces sympathoexcita tion by directly stimulating the central nervous system. It also has b een shown that nitric oxide (NO) may play a role in signal transductio n of the nervous system. Therefore, we hypothesized that the sympathoe xcitation of ketamine may be linked to central NO formation. To test t his hypothesis, we examined the effects of L-arginine, a substrate of NO formation, on renal sympathetic nerve activity (RSNA) during ketami ne anesthesia. Methods: Using 45 rabbits given basal anesthesia with a lpha-chloralose, we measured changes in heart rate, mean arterial pres sure, and RSNA in response to intravenous ketamine (1 mg/kg) and inves tigated the effect of intravenous L-arginine and D-arginine (bolus 30 mg/kg followed by continuous 30 mg.kg(-1).min(-1)). The animal were di vided into intact, sinoartic- and vagal-deafferented, and spinal cord- transected groups. Results: Ketamine caused significant increases in R SNA (172 +/- 16%), heart rate (12 +/- 2 beats/min), and mean arterial pressure (8 +/- 1 mmHg) in the intact rabbits. Ketamine also increases RSNA in sinoaortic- and vagal-deafferented rabbits, but not in spinal cord-transected rabbits. L-Arginine attenuated the ketamine-induced i ncrease in RSNA in intact and deafferented rabbits, whereas D-arginine had no effect on RSNA. In addition, N-G-nitro-L-arginine methyl ester , a NO synthase inhibitor, increased RSNA and the increase was attenua ted by L-arginine. Conclusion: Ketamine may act centrally to increase sympathetic outflow, and the sympathoexcitation may be attenuated by i ncreasing NO formation with L-arginine in the central nervous system.