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.
All Science Journal Classification (ASJC) codes
- Internal Medicine
- Cardiology and Cardiovascular Medicine