title: Proton magnetic resonance spectroscopy detection of neurotransmitters in dorsomedial medulla correlate with spontaneous baroreceptor reflex function.
abstract: Control of heart rate variability via modulation of sympathovagal balance is a key function of nucleus tractus solitarii and the dorsal motor nucleus of the vagus localized in the dorsomedial medulla oblongata. Normal blood pressure regulation involves precise balance of glutamate (Glu)-glutamine-gamma-aminobutyric acid transmitter systems, and angiotensin II modulates these transmitters to produce tonic suppression of reflex function. It is not known, however, whether other brain transmitters/metabolites are indicators of baroreflex function. This study establishes the concept that comprehensive baseline transmitter/metabolite profiles obtained using in vivo (1)H magnetic resonance spectroscopy in rats with well-characterized differences in resting blood pressure and baroreflex function can be used as indices of autonomic balance or baroreflex sensitivity. Transgenic rats with over-expression of renin [m(Ren2)27] or under-expression of glial-angiotensinogen (ASrAogen) were compared with Sprague-Dawley rats. Glu concentration in the dorsal medulla is significantly higher in ASrAogen rats compared with either Sprague-Dawley or (mRen2)27 rats. Glu levels and the ratio of Glu:glutamine correlated positively with indices of higher vagal tone consistent with the importance of these neurotransmitters in baroreflex function. Interestingly, the levels of choline-containing metabolites showed a significant positive correlation with spontaneous baroreflex sensitivity and a negative correlation with sympathetic tone. Thus, we demonstrate the concept that noninvasive assessment of neurochemical biomarkers may be used as an index of baroreflex sensitivity.
authors.affiliation: Department of Radiation Oncology, Wake Forest University School of Medicine, Hypertension and Vascular Research Center, Winston-Salem, NC 27157-1032, USA. mespinos@wfubmc.edu
authors.forename: Maria A
authors.initials: MA
authors.lastname: Garcia-Espinosa
authors.forename: Hossam A
authors.initials: HA
authors.lastname: Shaltout
authors.forename: John
authors.initials: J
authors.lastname: Olson
authors.forename: Brian M
authors.initials: BM
authors.lastname: Westwood
authors.forename: Mike E
authors.initials: ME
authors.lastname: Robbins
authors.forename: Kerry
authors.initials: K
authors.lastname: Link
authors.forename: Debra I
authors.initials: DI
authors.lastname: Diz
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001795:Blood Pressure Determination; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism* / Q000502:physiology; D009448:Neurochemistry; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents; D000804:Angiotensin II; D018698:Glutamic Acid