Role of ventrolateral medulla in sympatholytic effect of 8-OHDPAT in rats.
In halothane-anesthetized, paralyzed, and artificially ventilated rats, the putative 5-hydroxytryptamine1A receptor agonist 8-OHDPAT (13.1 micrograms/kg iv) produced hypotension (-14.6 +/- 1.3 mmHg, n = 35), reduced lumbar sympathetic nerve discharge (SND, -17.8%, n = 35), and slowed the discharge rate of sympathoexcitatory neurons recorded in the rostroventrolateral medulla (RVLM, -17.6%, n = 20). The gain of the baroreflex was unaffected by the drug, but SND and RVLM unit discharges were silenced at significantly reduced levels of mean arterial pressure (MAP; 153 vs. 171 mmHg for SND, 155 vs. 172 mmHg for RVLM cells). Subsequent intravenous administration of the alpha 2-adrenergic receptor agonist clonidine (5.3 micrograms/kg) produced an additional decrease in MAP (-21.2 +/- 1.9 mmHg, n = 24) and SND (-24%, n = 24), Bilateral microinjections of 8-OHDPAT into the RVLM (1 nmol/side, n = 9) or into the raphe pallidus-obscurus (2 injections of 1 nmol each, n = 7) also produced hypotension (-22.9 +/- 3.2 and -14.4 +/- 2.8 mmHg, respectively) and sympathoinhibition (-39.1 and -24.6%, respectively). Bilateral microinjection into RVLM of the alpha 2-adrenergic antagonists idazoxan (16 nmol/side, n = 6) or rauwolscine (2 nmol/side, n = 6) attenuated the sympatholytic effect of both 8-OHDPAT (13.1 micrograms/kg, iv) and clonidine (5.3 micrograms/kg iv). These results suggest that 8-OHDPAT may exert a portion of its central sympatholytic effect by activating alpha 2-adrenergic receptors in the rostroventral medulla.
Nosjean
A
A
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22908.
Guyenet
P G
PG
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D019329:Idazoxan; D008161:Lumbosacral Region; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects; D013565:Sympatholytics / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D013565:Sympatholytics; D013764:Tetrahydronaphthalenes; D015016:Yohimbine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003000:Clonidine; D019329:Idazoxan