title: Effects of angiotensin II type 1 receptor blocker and adiponectin on adipocyte dysfunction in stroke-prone spontaneously hypertensive rats.
abstract: BACKGROUND
  Hypoadiponectinemia in lipoatrophy may be related to worsening of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). One of the beneficial effects of candesartan (Angiotensin II Type 1 receptor blocker) for preventing hypertension may be increasing of adiponectin due to improvement of adipocyte dysfunction. In this study, we determined the effects of candesartan or adiponectin on pathophysiologic features and adipocyte dysfunction in SHRSP.
  
  
  METHODS
  Candesartan was administered to male SHRSP from 16 to 20 weeks of age (2 mg/kg/day). Adiponectin was cloned and intravenously administered to male SHRSP from 16 to 20 weeks of age. We examined biological parameters, as well as the expression and release of adipokines.
  
  
  RESULTS
  The SHRSP exhibited severe atrophy of visceral fat and progression of severe hypertension. The expression and release of leptin and adiponectin were impaired at 6 and 20 weeks of age. Candesartan suppressed the development of lipoatrophy and reduced the incidence of stroke at 20 weeks of age. Candesartan also enhanced the expression of adiponectin and leptin by inducing the overexpression of peroxisome proliferator activated receptor γ. Circulating level of leptin was significantly higher in candesartan group than in the control group, whereas adiponectin was similar in both groups. Intravenous administration of adiponectin resulted in enhancement of adiponectin expression in adipose tissue, but no remarkable effects were found in pathophysiology in SHRSP.
  
  
  CONCLUSIONS
  Our results indicate that candesartan protects against hypertension and adipocyte dysfunction in SHRSP. The induction of leptin expression appeared to be important factor in the inhibition of stroke lesions, whereas adiponectin was not a major regulator of blood pressure in SHRSP with genetic hypertension. Further studies are needed to elucidate the role of the renin-angiotensin system in adipose tissue dysfunction in relation to hypertensive end-organ damage.
authors.affiliation: Department of Food Science and Nutrition, Faculty of Agriculture, Kinki University, Nara, Japan. kuriman@nara.kindai.ac.jp
authors.forename: Kumiko
authors.initials: K
authors.lastname: Takemori
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin / Q000008:administration & dosage / Q000235:genetics*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D013777:Tetrazoles / Q000008:administration & dosage*
chemical_list: D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C081643:candesartan