title: Intrahypothalamic angiogenesis induced by osmotic stimuli correlates with local hypoxia: a potential role of confined vasoconstriction induced by dendritic secretion of vasopressin.
abstract: We have previously shown that hyperosmotic stimulation of adult Wistar rats induces local angiogenesis within hypothalamic magnocellular nuclei, in relation to the secretion of vascular endothelial growth factor (VEGF) by the magnocellular neurons. The present study aimed at understanding how osmotic stimulus relates to increased VEGF secretion. We first demonstrate a correlation between increased VEGF secretion and local hypoxia. Osmotic stimulation is known to stimulate the metabolic activity of hypothalamic magnocellular neurons producing arginine vasopressin (AVP) and to increase the secretion of AVP, both by axon terminals into the circulation and by dendrites into the extracellular space. In AVP-deficient Brattleboro rats, the dramatic activation of magnocellular hypothalamic neurons failed to induce hypoxia, VEGF expression, or angiogenesis, suggesting a major role of hypothalamic AVP. A possible involvement of dendritic AVP release is supported by the findings that 1) hypoxia and angiogenesis were not observed in non osmotically stimulated Wistar rats in which circulating AVP was increased by the prolonged infusion of exogenous AVP, 2) contractile arterioles afferent to the magnocellular nuclei were strongly constricted by the perivascular application of AVP via V1a receptors (V1a-R) stimulation, and 3) after the intracerebral or ip administrations of selective V1a-R antagonists to osmotically stimulated rats, hypothalamic hypoxia and angiogenesis were or were not inhibited, respectively. Together, these data strongly suggest that the angiogenesis induced by osmotic stimulation relates to tissue hypoxia resulting from the constriction of local arterioles, via the stimulation of perivascular V1a-R by AVP locally released from dendrites.
authors.affiliation: Institut de Génomique Fonctionnelle, Département d'Endocrinologie, 141 rue de la Cardonille, F-34094 Montpellier Cedex 05, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Alonso
authors.forename: Evelyne
authors.initials: E
authors.lastname: Gallibert
authors.forename: Chrystel
authors.initials: C
authors.lastname: Lafont
authors.forename: Gilles
authors.initials: G
authors.lastname: Guillon
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000098:blood supply* / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009995:Osmosis; D051381:Rats; D011910:Rats, Brattleboro; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D001127:Arginine Vasopressin