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(Hypertension. 1997;29:1173-1177.)
© 1997 American Heart Association, Inc.

Articles

Metformin Inhibits Ganglionic Neurotransmission in Renal Nerves

Jørgen S. Petersen; Wen Liu; Daniel R. Kapusta; ; Kurt J. Varner

From the Department of Pharmacology, The Panum Institute, University of Copenhagen, Denmark (J.S.P.), and Department of Pharmacology, Louisiana State University Medical Center, New Orleans.

Correspondence to Jørgen Søberg Petersen, MD, PhD, Department of Pharmacology, The Panum Institute, Bldg 18.6, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. E-mail fijsp{at}farmakol.ku.dk

Abstract Intravenous administration of the antihyperglycemic agent metformin decreases arterial pressure and sympathetic nerve activity (SNA). To test the hypothesis that metformin inhibits SNA by interrupting ganglionic neurotransmission, we compared the actions of intravenous administration of metformin and the ganglionic blocker trimethaphan on postganglionic renal and preganglionic adrenal sympathetic nerves in pentobarbital-anesthetized male Sprague-Dawley rats. Intravenous metformin elicited dose-dependent decreases in postganglionic renal SNA (1 mg/kg: 0±0%; 10 mg/kg: -20±4%; 100 mg/kg: -92±3%; n=7). Conversely, only the maximal dose of metformin affected preganglionic adrenal SNA (100 mg/kg: adrenal SNA=-14±6%; n=8). Ganglionic blockade with intravenous trimethaphan (5 mg/kg) produced a differential sympathoinhibitory response similar to the response observed after high-dose metformin (renal SNA=-100±3%; adrenal SNA=-17±7%; P<.001). Preganglionic renal neurons were electrically stimulated in the spinal cord, before and during the peak of the sympathoinhibitory response to intravenous metformin, and the magnitude of the stimulus-evoked increases in postganglionic renal SNA were compared. Metformin dose-dependently attenuated the magnitude of the increase in postganglionic renal SNA elicited by stimulation of the spinal cord (30 mg/kg: -23±8%; 90 mg/kg: -65±11%; 270 mg/kg: -91±8%; n=6 per dose). We conclude that high-dose intravenous metformin interrupts ganglionic neurotransmission in renal nerves.

Key Words: metformin • sympathetic nerve activity • neurotransmission • diabetes mellitus

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