Characterization of the sympathetic nerve responses to amphetamine: role of central alpha 2-adrenergic receptors.
Although amphetamine has profound cardiovascular actions, the role of the sympathetic nervous system in these responses is largely unknown. The purpose of this study was to characterize the sympathetic nerve responses to amphetamine and to determine whether these neural responses involve an action of amphetamine in the rostral ventrolateral medulla (RVLM). In sinoaortically denervated (SAD) and sham-SAD rats, amphetamine dose-dependently increased mean arterial pressure (MAP) and heart rate (HR), while decreasing (-87 +/- 5%, max) renal sympathetic nerve discharge (SND) for 57 +/- 5 min. Comparison of the SND responses in SAD and sham-SAD rats revealed a small but significant contribution of the baroreceptor reflex to the sympathoinhibitory response. In separate studies, the bilateral microinjection of amphetamine into RVLM decreased HR, MAP, and SND. The magnitude and duration of the decrease in SND elicited by amphetamine were significantly attenuated by the prior intravenous (i.v.) administration of idazoxan (alpha 2-adrenergic antagonist). The prior bilateral microinjection of idazoxan or piperoxan into RVLM significantly attenuated the duration of the sympathoinhibitory responses elicited by i.v. amphetamine. Idazoxan and piperoxan also tended to decrease the magnitude of the SND response; however, this reduction was significant at only the highest doses. The MAP and HR responses were unaffected by idazoxan treatment. The microinjection of terazosin (alpha 1-adrenergic antagonist) or propranolol (beta-adrenergic antagonist) into RVLM did not alter the HR, MAP, or SND responses to i.v. amphetamine. We conclude that i.v. amphetamine decreases SND in anesthetized rats, in large part, by a mechanism involving the activation of alpha 2-adrenergic receptors in RVLM.
Liu
W
W
Department of Pharmacology and Experimental Therapeutics, Louisana State University Medical Center, New Orleans 70112, USA.
Varner
K J
KJ
D018663:Adrenergic Agents / Q000494:pharmacology*; D058647:Adrenergic alpha-2 Receptor Agonists; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D019329:Idazoxan / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D010883:Piperoxan / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013566:Sympathomimetics / Q000494:pharmacology*
D018663:Adrenergic Agents; D058647:Adrenergic alpha-2 Receptor Agonists; D013566:Sympathomimetics; D010883:Piperoxan; D000661:Amphetamine; D019329:Idazoxan