Diabetic Hypertensive Leptin Receptor-Deficient db/db Mice Develop Cardioregulatory Autonomic Dysfunction

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dc.contributor.authorGoncalves, Andrey C. da Costa
dc.contributor.authorTank, Jens
dc.contributor.authorDiedrich, Andre
dc.contributor.authorHilzendeger, Aline Mourão [UNIFESP]
dc.contributor.authorPlehm, Ralph
dc.contributor.authorBader, Michael [UNIFESP]
dc.contributor.authorLuft, Friedrich C.
dc.contributor.authorJordan, Jens
dc.contributor.authorGross, Volkmar
dc.contributor.institutionMax Delbruck Ctr Mol Med
dc.contributor.institutionHannover Med Sch
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionVanderbilt Univ
dc.contributor.institutionHELIOS Klin
dc.date.accessioned2016-01-24T13:52:13Z
dc.date.available2016-01-24T13:52:13Z
dc.date.issued2009-02-01
dc.description.abstractLeptin receptor-deficient db/db mice develop human type 2 diabetes mellitus, hypertension, and obesity with disrupted circadian blood pressure (BP) rhythm. Whether leptin is the sole mechanism mediating autonomic imbalance and hypertension is unclear. To explore this notion further, we measured BP by radiotelemetry combined with fast Fourier transformation and assessed autonomic function pharmacologically before and after renin-angiotensin system blockade with enalapril. the resting period BP (117 +/- 3 versus 108 +/- 1.0 mm Hg) and heart rate (HR; 488 +/- 12 versus 436 +/- 8 bpm) were higher in db/db mice compared with db/+ mice. BP and HR amplitudes were lower in db/db mice compared with db/+ mice. BP response to trimetaphan (-43 +/- 5 versus -27 +/- 3 mm Hg) and HR response to metoprolol (-59 +/- 12 versus -5 +/- 4 bpm) were greater in db/db mice than in db/+ mice. the HR response to atropine was blunted in db/db mice (59 +/- 17 versus 144 +/- 24 bpm), as were baroreflex sensitivity and HR variability. Enalapril improved autonomic regulation in db/db mice. Stimulation of central alpha-2 adrenoreceptors enhanced both parasympathetic HR control and baroreflex sensitivity in db/db mice. We suggest that functional, rather than structural, alpha-2 adrenoceptor changes and the renin-angiotensin system are involved in the increased sympathetic and decreased parasympathetic tones in db/db mice. Our data suggest that db/db mice exhibit features found in humans with type 2 diabetic autonomic neuropathy and could serve as a model for this complication. (Hypertension. 2009; 53[part 2]: 387-392.)en
dc.description.affiliationMax Delbruck Ctr Mol Med, D-13125 Berlin, Germany
dc.description.affiliationHannover Med Sch, Inst Clin Pharmacol, D-3000 Hannover, Germany
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationVanderbilt Univ, Sch Med, Dept Med, Auton Dysfunct Serv,Div Clin Pharmacol, Nashville, TN 37212 USA
dc.description.affiliationHELIOS Klin, Franz Volhard Clin, Fac Med Charite, Berlin, Germany
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent387-392
dc.identifierhttp://dx.doi.org/10.1161/HYPERTENSIONAHA.108.124776
dc.identifier.citationHypertension. Philadelphia: Lippincott Williams & Wilkins, v. 53, n. 2, p. 387-392, 2009.
dc.identifier.doi10.1161/HYPERTENSIONAHA.108.124776
dc.identifier.issn0194-911X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/31271
dc.identifier.wosWOS:000262625400045
dc.language.isoeng
dc.publisherLippincott Williams & Wilkins
dc.relation.ispartofHypertension
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjecttype 2 diabetes mellitusen
dc.subjectobesityen
dc.subjecthypertensionen
dc.subjectACE inhibitionen
dc.subjectalpha-2 adrenoceptorsen
dc.subjectautonomic dysfunctionen
dc.titleDiabetic Hypertensive Leptin Receptor-Deficient db/db Mice Develop Cardioregulatory Autonomic Dysfunctionen
dc.typeinfo:eu-repo/semantics/article
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