title: Roles of brain angiotensin II and C-type natriuretic peptide in deoxycorticosterone acetate-salt hypertension in rats.
abstract: OBJECTIVE
  To investigate the roles of brain angiotensin II and C-type natriuretic peptide (CNP) in the hypertensive mechanism of deoxycorticosterone acetate (DOCA)-salt hypertension.
  
  
  METHODS
  We injected 50 microg/kg CV-11 974, an angiotensin II type-1 receptors antagonist, 30 nmol/kg CNP-22, or the vehicle (artificial cerebrospinal fluid) into the cerebral ventricle or intravenously 5 min before the intracerebroventricular infusion of 1.5 mol/I NaCl solution for 30 min into either male normotensive Wistar rats or DOCA-salt hypertensive rats anesthetized with urethane, and their arterial pressures and heart rates were continuously recorded. Blood (2 ml) was collected at the end of the infusion for the measurement of plasma concentration of arginine vasopressin. We infused 10 or 50 microg/kg per day CV-11 974, 10 or 50 nmol/kg per day CNP-22, or the vehicle (1 microl/h) into the cerebral ventricles of DOCA-salt hypertensive rats for 7 days by using osmotic minipumps, and measured their systolic arterial pressures, pulse rates, and urinary excretions of vasopressin.
  
  
  RESULTS
  Intracerebroventricular pre-administrations of CV-11 974 and of CNP-22 inhibited increases in mean arterial pressure, heart rate, and plasma vasopressin concentration induced by intracerebroventricular infusion of 1.5 mol/l NaCl into normotensive rats; increases in hemodynamics and plasma level of vasopressin induced by intracerebroventricular infusion of 1.5 mol/l NaCl were suppressed by intracerebroventricular pre-injections of CV-11 974, but not of CNP-22, into DOCA-salt hypertensive rats. Continuous intracerebroventricular infusions of 50 microg/kg per day CV-11 974 attenuated hypertension in DOCA-salt treated rats, accompanied by a reduction in urinary excretion of vasopressin. Continuous intracerebroventricular infusions of 50 nmol/kg per day CNP-22, however, affected neither hypertension nor urinary excretion of vasopressin in DOCA-salt hypertensive rats.
  
  
  CONCLUSIONS
  Brain angiotensin II could play a role in the pressor mechanism of DOCA-salt hypertension by increasing release of vasopressin via type 1 receptors. That brain CNP has an inhibitory effect on release of vasopressin in acute experiments indicates that the impairment of this inhibitory effect of brain CNP on secretion of vasopressin could be involved in the pathogenesis of DOCA-salt hypertension in rats.
authors.affiliation: Department of Clinical and Laboratory Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Ohtsuka
authors.forename: M
authors.initials: M
authors.lastname: Sakamoto
authors.forename: A
authors.initials: A
authors.lastname: Nanbu
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Yoshimura
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism / Q000652:urine; D001562:Benzimidazoles / Q000008:administration & dosage; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D003900:Desoxycorticosterone / Q000008:administration & dosage; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology*; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000008:administration & dosage / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000008:administration & dosage; D013777:Tetrazoles / Q000008:administration & dosage
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D001127:Arginine Vasopressin; D020098:Natriuretic Peptide, C-Type; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C081643:candesartan