Inhibition of renin-angiotensin system ameliorates endothelial dysfunction associated with aging in rats

Yasushi Mukai, Hiroaki Shimokawa, Midoriko Higashi, Keiko Morikawa, Tetsuya Matoba, Junko Hiroki, Ikuko Kunihiro, Hassan M A Talukder, Akira Takeshita

Research output: Contribution to journalArticle

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Abstract

Objective - Endothelial vasodilator functions are progressively impaired with aging, which may account in part for the increased incidence of cardiovascular events in elderly people. We examined what treatment could ameliorate the endothelial dysfunction associated with aging in rats. Methods and Results - Aged (12-month-old) Wistar-Kyoto rats were treated with vehicle, temocapril, CS-866 (an angiotensin II type 1 receptor antagonist), cerivastatin, or hydralazine for 2 weeks. Endothelium-dependent relaxations (EDRs) of aortas from aged rats were markedly impaired compared with EDRs of aortas from young (3-month-old) rats. Indomethacin, NS-398 (a cyclooxygenase [COX]-2 inhibitor), and SQ-29548 (a thromboxane A2/prostaglandin H2 receptor antagonist) acutely restored EDRs in aged rats, suggesting an involvement of COX-2-derived vasoconstricting eicosanoids. Tiron, a superoxide scavenger, also partially improved EDRs, suggesting an involvement of superoxide. EDRs were significantly ameliorated in aged rats after long-term treatment with temocapril or CS-866 but not after treatment with cerivastatin or hydralazine. Indomethacin induced no further improvement of EDRs after treatment with temocapril or CS-866. COX-2 protein expression and superoxide production were increased in the aortas of aged rats and were also attenuated by treatment with temocapril or CS-866. Conclusions - These results demonstrate that long-term inhibition of the renin-angiotensin system ameliorates endothelial dysfunction associated with aging through the inhibition of the synthesis of COX-2-derived vasoconstricting factors and superoxide anions.

Original languageEnglish
Pages (from-to)1445-1450
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 1 2002

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Renin-Angiotensin System
Endothelium
Superoxides
Cyclooxygenase 2
Aorta
Hydralazine
Indomethacin
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
Prostaglandin H2 Receptors Thromboxane A2
Angiotensin II Type 1 Receptor Blockers
Therapeutics
Inbred WKY Rats
Eicosanoids
Cyclooxygenase 2 Inhibitors
Vasodilator Agents
Olmesartan Medoxomil
temocapril hydrochloride
Incidence
Proteins

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Inhibition of renin-angiotensin system ameliorates endothelial dysfunction associated with aging in rats. / Mukai, Yasushi; Shimokawa, Hiroaki; Higashi, Midoriko; Morikawa, Keiko; Matoba, Tetsuya; Hiroki, Junko; Kunihiro, Ikuko; Talukder, Hassan M A; Takeshita, Akira.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 22, No. 9, 01.09.2002, p. 1445-1450.

Research output: Contribution to journalArticle

Mukai, Y, Shimokawa, H, Higashi, M, Morikawa, K, Matoba, T, Hiroki, J, Kunihiro, I, Talukder, HMA & Takeshita, A 2002, 'Inhibition of renin-angiotensin system ameliorates endothelial dysfunction associated with aging in rats', Arteriosclerosis, thrombosis, and vascular biology, vol. 22, no. 9, pp. 1445-1450. https://doi.org/10.1161/01.ATV.0000029121.63691.CE
Mukai, Yasushi ; Shimokawa, Hiroaki ; Higashi, Midoriko ; Morikawa, Keiko ; Matoba, Tetsuya ; Hiroki, Junko ; Kunihiro, Ikuko ; Talukder, Hassan M A ; Takeshita, Akira. / Inhibition of renin-angiotensin system ameliorates endothelial dysfunction associated with aging in rats. In: Arteriosclerosis, thrombosis, and vascular biology. 2002 ; Vol. 22, No. 9. pp. 1445-1450.
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