Significance of Angiotensin II Receptor Blocker Lipophilicities and Their Protective Effect against Vascular Remodeling

Autor: Yoshiki Mino, Katsuhiro Yoshikawa, Kazuyoshi Kirimura, Denan Jin, Mizuo Miyazaki, Shinji Takai, Michiko Muramatsu
Rok vydání: 2005
Předmět:
Carotid Artery Diseases
Male
Angiotensin receptor
Physiology
Gene Expression
Blood Pressure
Vasodilation
Pharmacology
Benzoates
Rats
Inbred WKY
chemistry.chemical_compound
Rats
Inbred SHR
Renin
Telmisartan
biology
Angiotensin II
Organ Size
Immunohistochemistry
Lipids
Losartan
NAD(P)H oxidase
Hypertension
cardiovascular system
Cardiology and Cardiovascular Medicine
hormones
hormone substitutes
and hormone antagonists
circulatory and respiratory physiology
medicine.drug
medicine.medical_specialty
Nitric Oxide Synthase Type III
Nitric oxide
Internal medicine
Internal Medicine
medicine
Animals
cardiovascular diseases
Myocardium
Body Weight
Membrane Transport Proteins
NADPH Oxidases
Phosphoproteins
Rats
Endocrinology
chemistry
biology.protein
Benzimidazoles
P22phox
Angiotensin II Type 1 Receptor Blockers
Zdroj: Hypertension Research. 28:593-600
ISSN: 1348-4214
0916-9636
DOI: 10.1291/hypres.28.593
Popis: Although the lipophilicities of the various angiotensin II receptor blockers (ARBs) are very different, the relationship between lipophilicity and the protective effect against vascular remodeling is unclear. In this study, we compared the protective effects of a highly lipophilic ARB, telmisartan, and an ARB with low lipophilicity, losartan, on vascular function and oxidative stress in stroke-prone spontaneously hypertensive rats (SHR-SP). SHR-SP received oral placebo, 1 mg/kg telmisartan, or 10 mg/kg losartan for 2 weeks. The blood pressure (BP) in SHR-SP was significantly higher than that in Wistar-Kyoto (WKY) rats before treatment, and the BP was reduced equally in telmisartan- and losartan-treated SHR-SP compared to placebo-treated SHR-SP. Acetylcholine-induced vasorelaxation in isolated carotid arteries was significantly weaker in SHR-SP than in WKY rats, but in both telmisartan- and losartan-treated SHR-SP, acetylcholine-induced vasorelaxation was significantly higher than in placebo-treated SHR-SP. Moreover, acetylcholine-induced vasorelaxation in telmisartan-treated rats was significantly stronger than in losartan-treated SHR-SP. The expression of the endothelial nitric oxide synthase gene was significantly higher in telmisartan- and losartan-treated rats than in placebo-treated SHR-SP, and was significantly higher in telmisartan-treated rats than in losartan-treated rats. In contrast, the expression of the NAD(P)H oxidase subunit p22phox gene in telmisartan-treated SHR-SP was significantly lower than that in losartan-treated SHR-SP. Immunohistochemistry showed that angiotensin II expression in the aorta was significantly lower in telmisartan-treated SHR-SP than in losartan-treated SHR-SP. In conclusion, a highly lipophilic ARB, telmisartan, may be useful for preventing NAD(P)H oxidase activity, and thereby for conferring vascular protection.
Databáze: OpenAIRE
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