| Metformin inhibits ganglionic neurotransmission in renal nerves. | |
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MedLine Citation:
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PMID: 9149683 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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: delta 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 (delta renal SNA = -100 +/- 3%; delta 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. |
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Authors:
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J S Petersen; W Liu; D R Kapusta; K J Varner |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Hypertension Volume: 29 ISSN: 0194-911X ISO Abbreviation: Hypertension Publication Date: 1997 May |
Date Detail:
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Created Date: 1997-06-03 Completed Date: 1997-06-03 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1173-7 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Panum Institute, University of Copenhagen, Denmark. fijsp@farmakol.ku.dk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Dose-Response Relationship, Drug Ganglionic Blockers / administration & dosage* Hypoglycemic Agents / administration & dosage* Injections, Intravenous Kidney / innervation*, physiopathology Male Metformin / administration & dosage* Rats Rats, Sprague-Dawley Sympathetic Nervous System / physiopathology* Synaptic Transmission / drug effects* Trimethaphan / administration & dosage* |
| Grant Support | |
ID/Acronym/Agency:
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DA 08255/DA/NIDA NIH HHS; DK 43337/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ganglionic Blockers; 0/Hypoglycemic Agents; 657-24-9/Metformin; 7187-66-8/Trimethaphan |
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