title: Anteroventral third ventricular N-methyl-D-aspartate receptors, but not metabotropic glutamate receptors are involved in hemorrhagic AVP secretion.
abstract: This study aimed to investigate the roles of glutamate (Glu) receptors in the anteroventral third ventricular region (AV3V), a pivotal area for water, cardiovascular and neuroendocrine regulations, in causing vasopressin (AVP) secretion and other phenomena in response to bleeding. The effects of intracerebral infusions of MK-801 [a N-methyl-D-aspartate (NMDA) receptor antagonist] or a metabotropic Glu receptor antagonist (MCPG) on plasma levels of AVP, electrolytes, osmolality and glucose, heart rate and arterial pressure following AV3V administration with NMDA or bleeding stimuli were analyzed in conscious rats. NMDA provoked prominent rises of plasma AVP, osmolality, glucose and arterial pressure, without changing plasma electrolytes or heart rate significantly. All the effects of NMDA were blocked by pre-administration of MK-801 into the same loci. Removal through a femoral arterial line of 10 ml blood per kg body weight did not affect arterial pressure or other variables significantly, although plasma AVP and angiotensin II (ANG II) tended to increase. When bleeding was repeated after 10 min (B2), arterial pressure dropped promptly, and plasma AVP, ANG II, osmolality and glucose augmented remarkably. MK-801 applied 35 min preceding B2, to loci such as the median preoptic nucleus, periventricular nucleus and medial preoptic area inhibited the response of plasma AVP significantly, without exerting any effects on other variables. When MK-801 was administered intracerebroventricularly, or when MCPG was infused into the AV3V, significant alterations did not occur in B2-evoked responses of plasma AVP nor in those of the other variables. In rats given sham bleeding after AV3V infusions of MK-801 or MCPG or intracerebroventricular applications of MK-801, all monitored variables roughly remained at stable levels throughout the experiments. We conclude that NMDA receptors in AV3V, but not metabotropic Glu receptors, may facilitate AVP secretion in hypotensive hypovolemia.
authors.affiliation: Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-Dori 1-757, Niigata City, Niigata 951-8510, Japan. kenbo@med.niigata-u.ac.jp
authors.forename: Ken'ichi
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D004573:Electrolytes / Q000097:blood; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006470:Hemorrhage / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D020542:Third Ventricle / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014667:Vasopressins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D014851:Wakefulness
chemical_list: D001786:Blood Glucose; D004573:Electrolytes; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C474696:methyl-(4-carboxyphenyl)glycine; D014667:Vasopressins; D000804:Angiotensin II; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D005998:Glycine