Role of presympathetic C1 neurons in the sympatholytic and hypotensive effects of clonidine in rats.
The rostral ventrolateral medulla (RVLM) may play an important role in the sympatholytic and hypotensive effects of clonidine. The present study examined which type of presympathetic RVLM neuron is inhibited by clonidine, and whether the adrenergic presympathetic RVLM neurons are essential for clonidine-induced sympathoinhibition. In chloralose-anesthetized and ventilated rats, clonidine (10 microg/kg iv) decreased arterial pressure (116 +/- 6 to 84 +/- 2 mmHg) and splanchnic nerve activity (93 +/- 3% from baseline). Extracellular recording and juxtacellular labeling of barosensitive bulbospinal RVLM neurons revealed that most cells were inhibited by clonidine (26/28) regardless of phenotype [tyrosine hydroxylase (TH)-immunoreactive cells: 48 +/- 7%; non-TH-immunoreactive cells: 42 +/- 5%], although the inhibition of most neurons was modest compared with the observed sympathoinhibition. Depletion of most bulbospinal catecholaminergic neurons, including 76 +/- 5% of the rostral C1 cells, by microinjection of saporin anti-dopamine beta-hydroxylase into the thoracic spinal cord (levels T2 and T4, 42 ng. 200 nl(-1). side(-1)) did not alter the sympatholytic or hypotensive effects of clonidine. These data show that although clonidine inhibits presympathetic C1 neurons, bulbospinal catecholaminergic neurons do not appear to be essential for the sympatholytic and hypotensive effects of systemically administered clonidine. Instead, the sympatholytic effect of clonidine is likely the result of a combination of effects on multiple cell types both within and outside the RVLM.
Schreihofer
A M
AM
Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908-0735, USA.
Guyenet
P G
PG
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002452:Cell Count; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D003000:Clonidine