Angiotensin II receptor antagonist improves age-related endothelial dysfunction.
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.
Kansui
Yasuo
Y
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Fujii
Koji
K
Goto
Kenichi
K
Abe
Isao
I
Iida
Mitsuo
M
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001685:Biological Factors / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004656:Enalapril / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014665:Vasodilator Agents / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001685:Biological Factors; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D004656:Enalapril; D000109:Acetylcholine; C077793:candesartan cilexetil