Targeted ablation of cardiac sympathetic neurons reduces resting, reflex and exercise-induced sympathetic activation in conscious rats.
Cholera toxin B subunit conjugated to saporin (SAP, a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected in both stellate ganglia to evaluate the physiological response to targeted ablation of cardiac sympathetic neurons. Resting cardiac sympathetic activity (cardiac sympathetic tonus), exercise-induced sympathetic activity (heart rate responses to graded exercise), and reflex sympathetic activity (heart rate responses to graded doses of sodium nitroprusside, SNP) were determined in 18 adult conscious Sprague-Dawley male rats. Rats were randomly divided into the following three groups (n = 6/group): 1) control (no injection), 2) bilateral stellate ganglia injection of unconjugated cholera toxin B (CTB), and 3) bilateral stellate ganglia injection of cholera toxin B conjugated to SAP (CTB-SAP). CTB-SAP rats, compared with control and CTB rats, had reduced cardiac sympathetic tonus and reduced heart rate responses to graded exercise and graded doses of SNP. Furthermore, the number of stained neurons in the stellate ganglia and spinal cord (segments T(1)-T(4)) was reduced in CTB-SAP rats. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing resting, exercise, and reflex sympathetic activity. Additional studies are required to further characterize the physiological responses to this procedure as well as determine if this new approach is safe and efficacious for the treatment of conditions associated with excess sympathetic activity (e.g., autonomic dysreflexia, hypertension, heart failure, and ventricular arrhythmias).
Lujan
Heidi L
HL
Department of Physiology, Wayne State Univ. School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA.
Palani
Gurunanthan
G
Chen
Ying
Y
Peduzzi
Jean D
JD
Dicarlo
Stephen E
SE
D000320:Adrenergic Fibers / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001370:Axonal Transport; D001794:Blood Pressure / Q000187:drug effects; D002772:Cholera Toxin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D005082:Physical Exertion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000076985:Saporins; D013233:Stellate Ganglion / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013563:Sympathectomy, Chemical; D013997:Time Factors
D054789:Ribosome Inactivating Proteins, Type 1; C420112:cholera toxin B-saporin conjugate; D009599:Nitroprusside; D002772:Cholera Toxin; D000076985:Saporins