Mechanisms underlying the sympathomimetic cardiovascular responses elicited by gamma-hydroxybutyrate.
Gamma-hydroxybutyrate (GHB) is generally thought to be a central nervous system depressant; however, GHB also has sympathomimetic cardiovascular actions. Radio telemetry was used to record the cardiovascular responses elicited by GHB (180-1000 mg/kg IV) in conscious rats. GHB elicited increases in mean arterial pressure (MAP) (24 +/- 3 to 60 +/- 5 mm Hg) lasting from 28 +/- 8 to 227 +/- 37 minutes. GHB (560 and 1000 mg/kg IV) also elicited a prolonged tachycardic response (85 +/- 23 and 95 +/- 22 bpm). The hypertension and tachycardia elicited by GHB (560 mg/kg) were reversed by the intravenous and intracerebroventricular administration of the GABAb receptor antagonist CGP 35348. CGP 35348 also reversed GHB-mediated increases in renal sympathetic nerve activity (RSNA). Administration of the purported GHB receptor antagonist NCS-382 reversed the increase in heart rate but not the pressor response elicited by GHB in telemetered rats. These data indicate that the intravenous administration of GHB markedly increases MAP, heart rate, and RSNA in conscious rats via activation of central GABAb receptors. In addition, GHB receptors appear to selectively mediate the increase in heart rate elicited by large doses of GHB.
Hicks
Alissa R
AR
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Kapusta
Daniel R
DR
Varner
Kurt J
KJ
D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001567:Benzocycloheptenes / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects; D012978:Sodium Oxybate / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects; D013566:Sympathomimetics / Q000494:pharmacology*; D013686:Telemetry
D018686:Anesthetics, Intravenous; D001567:Benzocycloheptenes; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; D013566:Sympathomimetics; C066471:NCS 382; D012978:Sodium Oxybate; C066430:CGP 35348