title: Effects of angiotensin II receptor antagonist on impaired endothelium-dependent and endothelium-independent relaxations in type II diabetic rats.
abstract: BACKGROUND
  Diabetes mellitus is an important risk factor for cardiovascular diseases, and vasodilator dysfunction may contribute to vascular complications in diabetes. We previously demonstrated that the angiotensin II receptor blocker (ARB) corrected the impaired endothelium-derived hyperpolarizing factor (EDHF)-mediated arterial hyperpolarization and relaxation associated with hypertension or aging, partially independently of blood pressure.
  
  
  OBJECTIVE
  To test whether EDHF-mediated, as well as endothelium-independent, relaxations would be altered in arteries from type II diabetic Goto-Kakizaki rats, and whether ARB would correct these alterations.
  
  
  METHODS
  Goto-Kakizaki rats were treated with either the ARB candesartan or a combination of hydralazine and hydrochlorothiazide for 8 weeks, beginning at 10 weeks of age. Membrane potentials and contractile responses were recorded from the isolated mesenteric arteries.
  
  
  RESULTS
  The two treatments lowered blood pressure comparably. Acetylcholine-induced, EDHF-mediated hyperpolarization and relaxation in mesenteric arteries were markedly impaired in untreated Goto-Kakizaki rats compared with age-matched Wistar rats, and neither ARB nor the combination therapy improved these responses. On the other hand, relaxations to endothelium-derived nitric oxide, assessed in rings precontracted with high potassium solution, were similar among the four groups. Relaxation to the nitric oxide donor sodium nitroprusside and that to levcromakalim, an ATP-sensitive K-channel opener, were also impaired in untreated Goto-Kakizaki rats, and the response to sodium nitroprusside was partially improved in treated Goto-Kakizaki rats.
  
  
  CONCLUSIONS
  These findings suggest that EDHF-mediated hyperpolarization and relaxation and endothelium-independent relaxations are both impaired in arteries of type II diabetic rats, and antihypertensive treatment with or without ARB partially corrects endothelium-independent relaxations to the nitric oxide donor but not EDHF-mediated responses.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Oniki
authors.forename: Koji
authors.initials: K
authors.lastname: Fujii
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kansui
authors.forename: Kenichi
authors.initials: K
authors.lastname: Goto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Iida
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006339:Heart Rate; D008564:Membrane Potentials; D051381:Rats; D017208:Rats, Wistar; D013599:Systole; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001685:Biological Factors; D001786:Blood Glucose; C067410:endothelium-dependent hyperpolarization factor