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Attenuation of Heart Rate Control and Neural Degeneration in Nucleus Ambiguus (NA) of OVE26 Transgenic Mice of Type 1 Diabetes
Author(s) -
yan binbin,
li Lihua,
Harden Scott W,
Cheng Zixi Jack
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.785.3
Subject(s) - baroreflex , endocrinology , nucleus ambiguus , medicine , microinjection , heart rate , vagus nerve , chemistry , blood pressure , mean arterial pressure , atenolol , anesthesia , central nervous system , medulla oblongata , stimulation
Baroreflex control of heart rate (HR) is impaired by diabetes mellitus. Previously, we found a deficit of central mediation of baroreflex‐bradycardia. In this study, we aimed to assess whether diabetes‐induced neural degeneration in NA and reduced HR response to microinjection of L‐Glutamate (L‐Glu) into the NA. FVB control and OVE26 diabetic mice (6mo) were anesthetized with sodium pentobarbital. HR and mean arterial blood pressure (MAP) responses to L‐Glu microinjections (0.1 0.2, 0.3, 0.4, 0.5, 1, 5 mMol/L, 20nl) into the left NA were measured. Brainstem slices ‐600, ‐300, 0, +300, and +600 μm relative to the obex were processed using Nissl staining. The NA region was identified by vagal motoneurons retrogradely‐labeled by TMR‐D injection into the ipsilateral nodose ganglion. Compared to FVB control, we found that: 1) diabetes attenuated the HR response (ΔHR: % of maximum) to L‐Glu injection into the NA at low doses (ANOVA, p<0.05, n=7/group), but MAP responses (ΔMAP: % of maximum) were unchanged. 2) After i.v. injection of β1‐bloker atenolol, ΔHR were reduced (to about 10% of the maximum HR response); subsequential injection of M‐blocker methylatropine, ΔHR were reduced additionally (to about 6.5% of the maximum HR response) in both FVB and OVE26 mice. 3) Diabetes reduced the number of vagal motoneurons in the NA region [the total number of NA motoneurons (left and right): 299.3 ± 17.8 (FVB) vs. 182.2 ± 13.6 (OVE26); p <0.05; n=6/group]. We suggest that degeneration of NA motoneurons may contribute to impairment of baroreflex sensitivity in OVE26 mice. Supported by NIH HL79636.