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Therefore, the objective of this study was to examine whether acute administration of metformin produces changes in mean arterial pressure, heart rate, or efferent renal sympathetic nerve activity in spontaneously hypertensive rats. Rats were anesthetized with alphaxalone-alphadolone (Saffan), paralyzed with pancuronium, and artificially ventilated. Intravenous administration of metformin (0, 1, 10, 100 mg\/kg) produced dose-dependent reversible decreases in mean arterial pressure, heart rate, and efferent renal sympathetic nerve activity that were not affected by arterial or cardiopulmonary baroreceptor denervation, nitric oxide synthase inhibition by<jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>-nitro-<jats:sc>l<\/jats:sc>-arginine methyl ester, or cyclooxygenase inhibition by indomethacin. Metformin given into the lateral cerebral ventricle (250, 500, 1000 \u03bcg) produced dose-dependent decreases in mean arterial pressure, heart rate, and efferent renal sympathetic nerve activity in doses that caused no changes when given intravenously. The sympathoinhibitory response to intracerebroventricular administration of metformin was not affected by \u03b1<jats:sub>2<\/jats:sub>-adrenoceptor blockade by intracerebroventricular yohimbine. We conclude that metformin has acute sympathoinhibitory effects (decreased arterial pressure, heart rate, and efferent renal sympathetic nerve activity) that are produced by a direct central nervous system site of action.<\/jats:p>","DOI":"10.1161\/01.hyp.27.3.619","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"619-625","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Acute Sympathoinhibitory Actions of Metformin in Spontaneously Hypertensive Rats"],"prefix":"10.1161","volume":"27","author":[{"given":"J\u00f8rgen S.","family":"Petersen","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, The Panum Institute, University of Copenhagen (Denmark) (J.S.P.), and Department of Internal Medicine, University of Iowa College of Medicine and Veterans Administration Medical Center, Iowa City (G.F.D.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald F.","family":"DiBona","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, The Panum Institute, University of Copenhagen (Denmark) (J.S.P.), and Department of Internal Medicine, University of Iowa College of Medicine and Veterans Administration Medical Center, Iowa City (G.F.D.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.310.6972.83"},{"key":"e_1_3_2_2_2","first-page":"95","volume":"1","year":"1979","unstructured":"Montaguti U, Celin D, Ceredi C, Descovich GC. 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