Alpha 2-adrenoceptor-mediated inhibition of bulbospinal barosensitive cells of rat rostral medulla.
Bulbospinal barosensitive neurons of the rostral ventrolateral medulla (RVLM cells; presumed sympathetic vasomotor premotor neurons) were recorded with iontophoretic electrodes in urethan-anesthetized rats. The majority of these cells were insensitive to intravenous clonidine (Clo; up to 20 micrograms/kg) and insensitive to iontophoretically applied Clo or alpha-methylnorepinephrine (alpha-MNE). These cells (n = 47 of 76) had a spinal conduction velocity of 4.1 +/- 0.2 m/s and a mean firing rate of 20 +/- 1 spikes/s. A second population (n = 29) was powerfully inhibited by intravenous Clo (5-10 micrograms/kg, activity decreased by 83 +/- 11%), iontophoretically applied Clo (decreased by 51 +/- 7%), and iontophoresis of alpha-MNE (decreased by 69 +/- 3%). These cells had a slower conduction velocity (2.0 +/- 0.3 m/s) and a much slower discharge rate (6 +/- 1 spikes/s). Both populations were pulse synchronous at resting arterial pressure. The inhibitory effects produced by iontophoresis of alpha-MNE or Clo were reduced to the same degree (86-98%) by iontophoresis of idazoxan (an alpha 2-adrenergic antagonist with imidazoline structure) and by iontophoresis of piperoxan (65-77%, a nonimidazoline alpha 2-antagonist). The inhibition of RVLM cells by intravenous Clo was reversed by iontophoresis of idazoxan and by intravenous injection of yohimbine (nonimidazoline alpha 2-antagonists). These data suggest that 1) intravenous Clo only inhibits a subpopulation of RVLM sympathetic premotoneurons, possibly the C1 adrenergic cells, 2) this effect of Clo is due to activation of alpha 2-adrenergic receptors rather than nonadrenergic imidazoline binding sites, and 3) these alpha 2-receptors are located on or close to the Clo-sensitive cells and may be continuously activated by endogenously released catecholamines.
Allen
A M
AM
Department of Pharmacology, University of Virginia, Charlottesville 22908.
Guyenet
P G
PG
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D019329:Idazoxan; D007275:Injections, Intravenous; D007478:Iontophoresis; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D008771:Nordefrin / Q000008:administration & dosage / Q000494:pharmacology*; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D005680:gamma-Aminobutyric Acid; D003000:Clonidine; D008771:Nordefrin; D019329:Idazoxan