Sympathetic reflexes after depletion of bulbospinal catecholaminergic neurons with anti-DbetaH-saporin.
We examined the effects of destroying bulbospinal catecholaminergic neurons with the immunotoxin anti-dopamine beta-hydroxylase-saporin (anti-DbetaH-Sap) on splanchnic nerve activity (SNA) and selected sympathetic reflexes in rats. Anti-DbetaH-Sap was administered into the thoracic spinal cord with the retrograde tracer fast blue. After 3-5 wk, anti-DbetaH-Sap eliminated most bulbospinal C1 (>74%), C3 ( approximately 84%), A5 ( approximately 98%), and A6 cells. Noncatecholaminergic bulbospinal neurons of the rostral ventrolateral medulla and serotonergic neurons were spared. Under chloralose anesthesia, mean arterial pressure and heart rate of anti-DbetaH-Sap-treated rats (3-5 wk) were normal. Resting SNA was not detectably altered, but the baroreflex range and gain were reduced approximately 40% (P < 0.05). Phenyl biguanide-induced decreases in mean arterial pressure, heart rate, and SNA were unchanged by anti-DbetaH-Sap, but the sympathoexcitatory response to intravenous cyanide was virtually abolished (P < 0.05). Rats that received spinal injections of saporin conjugated to an anti-mouse IgG had intact bulbospinal C1 and A5 cells and normal physiological responses. These data suggest that C1 and A5 neurons contribute modestly to resting SNA and cardiopulmonary reflexes. However, bulbospinal catecholaminergic neurons appear to play a prominent sympathoexcitatory role during stimulation of chemoreceptors.
Department of Pharmacology, University of Virginia, Charlottesville 22908, USA.
A M
AM
Schreihofer
P G
PG
Guyenet
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D001158:Arteries / Q000502:physiology; D017704:Baroreflex / Q000502:physiology; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D002452:Cell Count / Q000187:drug effects; D005456:Fluorescent Dyes / Q000494:pharmacology; D000922:Immunotoxins / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012966:Sodium Cyanide / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013153:Splanchnic Nerves / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*
D000578:Amidines; D000911:Antibodies, Monoclonal; D001645:Biguanides; D002395:Catecholamines; D005456:Fluorescent Dyes; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; C101397:anti-dopamine beta-hydroxylase immunotoxin; C031455:diamidino compound 253-50; D000076985:Saporins; D012966:Sodium Cyanide; C008846:phenyl biguanide