title: Decreased susceptibility to salt-induced hypertension in subtotally nephrectomized mice lacking the vasopressin V1a receptor.
abstract: OBJECTIVE
  By examining vasopressin V1a receptor (V1aR) knockout (KO) mice, we previously found that the V1aR is critically involved in the regulation of normal blood pressure. The present study was undertaken to elucidate the role of the V1aR in salt-induced hypertension.
  
  
  RESULTS
  We compared haemodynamic responses induced by subtotal nephrectomy + salt loading in V1aR KO mice with those of wild-type (WT) controls. The time course of changes in the systolic blood pressure and heart rate during the salt loading was attenuated in the KO mice compared with that for the WT mice. The elevation of the plasma norepinephrine level caused by the subtotal nephrectomy + salt loading was also reduced in the V1aR KO mice. A V1aR antagonist markedly lowered the arterial blood pressure in the salt-loaded WT mice but not in the normotensive WT mice or in the salt-loaded or normotensive V1aR KO mice. Whereas arginine vasopressin (AVP) administered to the lateral ventricle of the brain induced pressor and tachycardiac responses accompanied by sympathetic activation in the WT mice, these events were completely abolished in the V1aR KO mice. Also, pressor and tachycardiac responses induced by intraventricularly administered hypertonic saline in the WT mice were diminished in the V1aR KO mice. Moreover, the pressor response induced by intraventricularly administered AVP was reduced in alpha(1d) adrenoceptor KO mice, whereas the tachycardiac response did not differ from that of the WT mice.
  
  
  CONCLUSIONS
  These results suggest that the V1aR is involved in the elevation of arterial blood pressure caused by dietary salt and that a V1aR antagonist, in particular regarding its effect in the brain, could have significant therapeutic potential in the treatment of hypertension.
authors.affiliation: Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Oikawa
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hosoda
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nasa
authors.forename: Takuya
authors.initials: T
authors.lastname: Daicho
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Norio
authors.initials: N
authors.lastname: Takagi
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tanonaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeo
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000031:analogs & derivatives; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate; D006727:Hormone Antagonists / Q000008:administration & dosage; D006973:Hypertension / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009392:Nephrectomy; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency / Q000235:genetics; D017483:Receptors, Vasopressin / Q000172:deficiency* / Q000235:genetics; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage; D012964:Sodium / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014661:Vasoconstriction
chemical_list: C547720:Adra1d protein, mouse; D006727:Hormone Antagonists; D018340:Receptors, Adrenergic, alpha-1; D017483:Receptors, Vasopressin; D012462:Saline Solution, Hypertonic; D017673:Sodium Chloride, Dietary; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D012964:Sodium