title: Chronic reductions in carotid blood flow cause salt-sensitive hypertension in rats.
abstract: OBJECTIVE
  We determined whether chronic reductions in carotid blood flow elicit salt-sensitive hypertension through regulation of the brain renin-angiotensin system (RAS).
  
  
  METHODS
  Both internal carotid arteries of male Wistar rats were ligated over a 1-week period. Carotid-ligated or sham-operated rats were treated with a high-salt (8% NaCl diet and 1% NaCl drinking water) or low-salt (0.3% NaCl diet and distilled water) diet for 6 weeks. At the end of the experiment, expression of the RAS mRNAs in the brain was measured. Effects of a 6-day intracerebroventricular infusion of CV-11974, a selective non-peptide angiotensin II type 1 (AT1) receptor blocker, were investigated in carotid-ligated rats administered high-salt diet.
  
  
  RESULTS
  High-salt administration increased systolic arterial pressure compared with low-salt administration in sham-operated rats [168 +/- 4 mmHg (n = 10) versus 149 +/- 3 mmHg (n = 10), P < 0.001] and in carotid-ligated rats [202 +/- 5 mmHg (n = 10) versus 153 +/- 2 mmHg (n = 10), P < 0.0001]. Systolic arterial pressure, urinary excretion of vasopressin and norepinephrine, and expression of renin, angiotensin I converting enzyme, and AT1 receptor mRNAs in the hypothalamus were greater in carotid-ligated rats than in sham-operated rats treated with high salt. In contrast, these parameters did not differ between carotid-ligated and sham-operated rats treated with low salt. Intracerebroventricular infusion of CV-11974 abolished the increase in these parameters in carotid-ligated rats treated with the high-salt diet.
  
  
  CONCLUSIONS
  Chronic reductions in carotid blood flow may cause salt-sensitive hypertension in normotensive rats by activating the hypothalamic RAS.
authors.affiliation: Cardiovascular Division, Toujinkai Hospital, Kyoto, Japan. mnishimura@tea.ocn.ne.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Nishimura
authors.forename: Hakuo
authors.initials: H
authors.lastname: Takahashi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ono
authors.forename: Manabu
authors.initials: M
authors.lastname: Yoshimura
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure; D002339:Carotid Arteries / Q000502:physiology*; D002560:Cerebrovascular Circulation; D015870:Gene Expression; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D007031:Hypothalamus / Q000502:physiology; D008026:Ligation; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D007703:Peptidyl-Dipeptidase A; D012083:Renin; C081643:candesartan