title: Mechanism of the cardiovascular effects of the GABAA receptors of the ventral tegmental area of the rat brain.
abstract: The ventral tegmental area (VTA) contains GABA terminals involved in the regulation of the cardiovascular system. Previously, we demonstrated that blocking GABAA but not GABAB receptors produced a pressor response accompanied by marked bradycardia. This study was performed to find the possible mechanisms involved in these responses by blocking ganglionic nicotinic receptors, peripheral muscarinic receptors or peripheral V1 vasopressin receptors. Experiments were performed on urethane anesthetized male Wistar rats. Drugs were microinjected unilaterally into the VTA (100 nl). The average changes in mean arterial pressure (MAP) and heart rate (HR) were compared between pre- and post-treatment using paired t-test. Injection of bicuculline methiodide (BMI), a GABAA antagonist, into the VTA caused a significant increase in MAP and a decrease in HR. Administration (i.v.) of the nicotinic receptor blocker, hexamethonium, enhanced the pressor response but abolished the bradycardic response to BMI, which ruled out involvement of the sympathetic nervous system. Blockade of the peripheral muscarinic receptors by homatropine (i.v.) abolished the bradycardic effect of BMI, but had no effect on the pressor response, indicating that bradycardia was produced by the parasympathetic outflow to the heart. Both the pressor and bradycardic responses to BMI were blocked by V1 receptor antagonist (i.v.), indicating that administration of BMI in the VTA disinhibited the release of vasopressin into the circulation. In conclusion, we demonstrated that GABAergic mechanism of the VTA exerts a tonic inhibition on vasopressin release through activation of GABAA receptors. The sympathetic system is not involved in the decrease of blood pressure by GABA of the VTA.
authors.affiliation: Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Fahimeh
authors.initials: F
authors.lastname: Yeganeh
authors.affiliation: Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Ranjbar
authors.affiliation: Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: mahatm@sums.ac.ir.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Hatam
authors.affiliation: Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Nasimi
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D005725:Ganglia, Autonomic / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D014326:Tropanes / Q000494:pharmacology; D014667:Vasopressins / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D058787:GABA-A Receptor Antagonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011963:Receptors, GABA-A; D014326:Tropanes; D014667:Vasopressins; D018738:Hexamethonium; C100236:homatropine; D001640:Bicuculline
keywords: Blood pressure; GABA; Heart rate; Vasopressin; Ventral tegmental area