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Cardiovascular and Neurophysiological Assessment of Guanethidine‐Induced Loss of Postganglionic Neurons in Male Sprague Dawley Rats
Author(s) -
Zahner Matthew,
Bernardo Vincent,
Tyszkiewicz Cheryl,
Foote Adrianne,
Can Keri,
Liu ChangNing,
Okerberg Carlin,
Boucher Magalie,
Pardo Ingrid,
Somps Chris,
Northcott Carrie
Publication year - 2015
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.29.1_supplement.831.2
Subject(s) - guanethidine , neurophysiology , medicine , neuroscience , endocrinology , psychology , stimulation
During postganglionic depletion there are a number of physiological compensatory mechanisms that maintain cardiovascular (CV) hemodynamic control. However, there is limited understanding at what point sympathetic noradrenergic postganglionic depletion results in changes to CV hemodynamics. To investigate these relationships two experimental paradigms were designed. Guanethidine was used to pharmacologically diminish the postganglionic sympathetic neurons. Rats received daily IP injections of vehicle or guanethidine (100 mg/kg/day) for either 5 or 11 days with an additional 20 day recovery period following respective treatments. Evaluations of conscious measures of heart rate (HR), blood pressure (BP), activity, temperature, cardiac baroreceptor (BR) responsiveness, urinalysis (for catecholamine metabolite, 3‐methoxy‐4‐hydroxyphenylethylenglycol; MHPG) and pupillometry assessments were performed. Following 5 days of guanethidine/recovery, there was a decrease in creatinine‐normalized urine MHPG levels compared to vehicle controls (47%); however no other parameter evaluated differed from vehicle. Interestingly, following 11 days of guanethidine/recovery, there was not only decreased urine MHPG levels (67%), but also significant decreases in systolic and mean BP (‐9 and ‐5 mm Hg, respectively; p<0.05), decreases in the pupil/iris ratio (19%; p<0.05), and diminished BR‐mediated reflex tachycardia responses during BR testing (p<0.05). These data suggest that there is a threshold of postganglionic depletion required to elicit changes in physiological CV parameters.