Vol. 188, No. 1, 1992 October 15, 1992 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 330-335 INSULIN INHIBITS NOREPINEPHRINE OVERFLOW FROM PERIPHERAL SYMPATHETIC NERVE ENDING Tatsuo Shimosawa, Katsuyuki Ando, Ayumu Ono, Katsutoshi Takahashi, Masashi Isshiki, Miki Kanda, Etsuro Ogata, and Toshiro Fujita Fourth Department of Internal Medicine, University of Tokyo School Of Medicine,Tokyo 112, Japan Received September 7, 1992 Summary;The effectsof insulin on peripheral nervous system are unknown. We therefore studied the effects of insulin on sympathetic nerve activity in isolated mesenteric arteries of Sprague-Dawley rats. The overflow of norepinephrine (NE) by electrical stimulation was used as the index of sympathetic nervous system activity. Insulin (0.5 to 1 U/I) decreased the NE release in a dose-dependent fashion. This inhibitory effect was, however, reversed by either 5x1 Om5 M cocaine or 5x1 O-4 M ouabain treatment. Thus, we postulate that insulin attenuates NE overflow from peripheral sympathetic nerve endings, probably due to enhanced NE reuptake. 0 1992 Academic Press, Inc. Norepinephrine (NE) release is influenced not only by reflexes via the central nervous system but also by local action of modulators in peripheral nerve endings. It has been demonstrated that systemic administration of insulin increases plasma NE level in humans (l), although the precise mechanism is unknown. This increased plasma NE by systemic insulin administration may be due to insulin effects on the central or peripheral systems. This study was therefore performed to determine the effect of insulin on NE release from peripheral nerve endings in the mesenteric arteries of rats. nals and Methods The mesenteric arteries of 8 to 9 week-old male Sprague-Dawley rats were isolated by a modification of Castellucci’s method (2). The intestine was discarded and mesenteric arteries were promptly connected to the perfusion apparatus. The preparations were perfused with Krebs-Henseleit solution with 400mg/l of bovine serum albumin by use of a peristaltic pump (3mVmin). Constituents of this solution were as follows (mmol/l): NaCI, 114.5; KCI, 4.6; KHsP04, 1.4; MgS04,2.4; CaCh, 2.5; NaHCOs, 25; Glucose 5.6. The solution was continuously oxygenated with a gas mixture of 95% 0~5% Co;! at 37°C. Platinum electrodes placed around the peri-arterial plexi of the mesenteric arteries were used to stimulate the sympathetic nerves. A standard 0006-291X/92 $4.00 Copyright 0 I992 by Academic Press, Inc. All rights of reproduction in any form reserved. 330