Angiotensin II receptor antagonist improves age-related endothelial dysfunction

Yasuo Kansui, Koji Fujii, Kenichi Goto, Isao Abe, Mitsuo Iida

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background. We previously demonstrated that the angiotensin converting enzyme (ACE) inhibitor, enalapril, prevents the age-related impairment of endothelium-dependent hyperpolarization and relaxation mediated by endothelium-derived hyperpolarizing factor (EDHF). Objective. To test whether angiotensin II type 1 (AT1) receptor antagonists would also improve age-related endothelial dysfunction. Methods. Normotensive Wistar-Kyoto (WKY) rats were treated for 3 months with either the AT1 receptor antagonist, candesartan cilexetil (3.5 mg/kg per day; candesartan group), or the ACE inhibitor, enalapril (20 mg/kg per day; enalapril group), from 9 to 12 months of age. Untreated 12-month-old WKY rats (old group) served as controls (n = 7-12). Results. The two treatments decreased systolic blood pressure comparably. EDHF-mediated hyperpolarization in response to acetylcholine (ACh; 10-5 mol/l) in the presence of norepinephrine in mesenteric arteries was improved in both the candesartan and enalapril groups to a similar extent compared with the old group (candesartan group, -24 ± 3 mV; enalapril group, -21 ± 2 mV; old group, -13 ± 2 mV). EDHF-mediated relaxation was similarly improved in the candesartan and enalapril groups (maximum relaxation: candesartan group, 70 ± 7%; enalapril group, 63 ± 8%; old group, 33 ± 9%). Hyperpolarization and relaxation responses to levcromakalim, an ATP-sensitive K+-channel opener, were similar in all groups. Conclusions. These findings suggest that the AT1 receptor antagonist is as effective as the ACE inhibitor in improving the age-related decline in EDHF-mediated hyperpolarization and relaxation in normotensive rats. Thus AT1 receptor antagonists might serve as novel tools with which to prevent endothelial dysfunction associated with aging.

Original languageEnglish
Pages (from-to)439-446
Number of pages8
JournalJournal of hypertension
Volume20
Issue number3
DOIs
Publication statusPublished - Mar 2002

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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