title: Chronic central leptin infusion restores cardiac sympathetic-vagal balance and baroreflex sensitivity in diabetic rats.
abstract: This study tested whether leptin restores sympathetic-vagal balance, heart rate (HR) variability, and cardiac baroreflex sensitivity (BRS) in streptozotocin (STZ)-induced diabetes. Sprague-Dawley rats were instrumented with arterial and venous catheters, and a cannula was placed in the lateral ventricle for intracerebroventricular (ICV) leptin infusion. Blood pressure (BP) and HR were monitored by telemetry. BRS and HR variability were estimated by linear regression between HR and BP responses to phenylephrine or sodium nitroprusside and autoregressive spectral analysis. Measurements were made during control period, 7 days after induction of diabetes, and 7 days after ICV leptin infusion. STZ diabetes was associated with hyperglycemia (422 +/- 17 mg/dl) and bradycardia (-79 +/- 4 beats/min). Leptin decreased glucose levels (165 +/- 16 mg/dl) and raised HR to control values (303 +/- 10 to 389 +/- 10 beats/min). Intrinsic HR (IHR) and chronotropic responses to a full-blocking dose of propranolol and atropine were reduced during diabetes (260 +/- 7 vs. 316 +/- 6, -19 +/- 2 vs. -43 +/- 6, and 39 +/- 3 vs. 68 +/- 8 beats/min), and leptin treatment restored these variables to normal (300 +/- 7, -68 +/- 10, and 71 +/- 8 beats/min). Leptin normalized BRS (bradycardia, -2.6 +/- 0.3, -1.7 +/- 0.2, and -3.0 +/- 0.5; and tachycardia, -3.2 +/- 0.4, -1.9 +/- 0.3, and -3.4 +/- 0.3 beats.min(-1).mmHg(-1) for control, diabetes, and leptin) and HR variability (23 +/- 4 to 11 +/- 1.5 ms2). Chronic glucose infusion to maintain hyperglycemia during leptin infusion did not alter the effect of leptin on IHR but abolished the improved BRS. These results show rapid impairment of autonomic nervous system control of HR after the induction of diabetes and that central nervous system actions of leptin can abolish the hyperglycemia as well as the altered IHR and BRS in STZ-induced diabetes.
authors.affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216-4505, USA. jdocarmo@physiology.umsmed.edu
authors.forename: Jussara M
authors.initials: JM
authors.lastname: do Carmo
authors.forename: John E
authors.initials: JE
authors.lastname: Hall
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: da Silva
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004435:Eating; D006321:Heart / Q000294:innervation*; D006339:Heart Rate; D015918:Infusion Pumps, Implantable; D007263:Infusions, Parenteral; D020738:Leptin / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D020738:Leptin; D018727:Muscarinic Antagonists
references.citation: Diabetes. 2002 Mar;51(3):778-83
references.pmid: 11872679
references.citation: Hypertension. 1998 Jan;31(1 Pt 2):409-14
references.pmid: 9453337
references.citation: Cardiovasc Res. 2000 Mar;45(4):889-99
references.pmid: 10728415
references.citation: Braz J Med Biol Res. 2002 Jul;35(7):843-9
references.pmid: 12131926
references.citation: Diabetes. 1999 Sep;48(9):1706-12
references.pmid: 10480598
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1275-82
references.pmid: 16778068
references.citation: Hypertens Res. 2003 Dec;26(12):991-8
references.pmid: 14717342
references.citation: Hypertension. 1997 Sep;30(3 Pt 2):619-23
references.pmid: 9322991
references.citation: Am J Physiol. 1994 Jan;266(1 Pt 2):H235-43
references.pmid: 8304504
references.citation: Am J Physiol. 1997 Dec;273(6):H2876-83
references.pmid: 9435627
references.citation: Hypertension. 2004 Jun;43(6):1312-7
references.pmid: 15123576
references.citation: Endocrinology. 1999 May;140(5):2117-24
references.pmid: 10218962
references.citation: Nature. 1999 Sep 2;401(6748):73-6
references.pmid: 10485707
references.citation: J Auton Nerv Syst. 1998 Mar 3;69(1):21-30
references.pmid: 9672120
references.citation: Diabetes. 1982 Aug;31(8 Pt 1):730-7
references.pmid: 6761211
references.citation: J Clin Invest. 1986 Aug;78(2):366-74
references.pmid: 3734097
references.citation: Diabetes. 1999 Feb;48(2):287-91
references.pmid: 10334303
references.citation: Diabetes. 1997 Dec;46(12):2040-3
references.pmid: 9392493
references.citation: Exp Physiol. 2005 Mar;90(2):237-45
references.pmid: 15640274
references.citation: Am J Hypertens. 2006 Feb;19(2):153-60
references.pmid: 16448885
references.citation: Lancet. 1978 Jan 7;1(8054):14-6
references.pmid: 74496
references.citation: Diabetes. 2000 Feb;49(2):244-52
references.pmid: 10868941
references.citation: Am J Physiol. 1994 Jan;266(1 Pt 2):H244-9
references.pmid: 8304505
references.citation: Metabolism. 2004 Dec;53(12):1558-64
references.pmid: 15562400
references.citation: Brain Res. 1993 Dec 3;629(2):342-4
references.pmid: 8111638
references.citation: MMWR Morb Mortal Wkly Rep. 2007 Mar 2;56(8):161-5
references.pmid: 17332726
references.citation: Am J Physiol. 1997 Oct;273(4):H1888-93
references.pmid: 9362257
references.citation: Hypertension. 2006 Jul;48(1):58-64
references.pmid: 16754792
references.citation: Hypertension. 1995 Dec;26(6 Pt 2):1100-4
references.pmid: 7498976
references.citation: J Electrocardiol. 2001 Jul;34(3):243-50
references.pmid: 11455515
references.citation: J Physiol. 2000 Jul 15;526 Pt 2:387-96
references.pmid: 10896727
references.citation: Nature. 2000 Apr 6;404(6778):661-71
references.pmid: 10766253
references.citation: Braz J Med Biol Res. 1997 Sep;30(9):1081-6
references.pmid: 9458968
references.citation: N Engl J Med. 2002 Feb 21;346(8):570-8
references.pmid: 11856796
references.citation: Hypertension. 2002 Feb;39(2 Pt 2):496-501
references.pmid: 11882597
references.citation: Diabetologia. 2001 Apr;44(4):464-70
references.pmid: 11357477
references.citation: J Clin Endocrinol Metab. 2008 Jan;93(1):26-31
references.pmid: 17940115
references.citation: J Endocrinol. 1993 Dec;139(3):479-86
references.pmid: 7907647
references.citation: J Neurosci. 2003 Jul 9;23(14):5998-6004
references.pmid: 12853417
references.citation: J Mol Cell Cardiol. 1986 Jun;18(6):617-24
references.pmid: 3525850
references.citation: Hypertension. 1997 Sep;30(3 Pt 2):632-5
references.pmid: 9322994