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Significance of angiotensin II receptor blockers with high affinity to angiotensin II type 1 receptors for vascular protection in rats.
Hypertens Res. 2009 Oct; 32(10):853-60.HR

Abstract

Angiotensin II receptor blockers (ARBs) vary in their binding affinities to angiotensin II type 1 (AT(1)) receptors in in vitro experiments. We compared a high-affinity ARB, olmesartan, and a low-affinity ARB, valsartan, in terms of their vascular protective effects in stroke-prone spontaneously hypertensive rats (SHR-SP). Blood pressure was equally reduced by placebo, olmesartan (1 mg kg(-1)) and valsartan (3 mg kg(-1)) daily for 2 weeks. In another experiment, 12-week-old SHR-SP were fed 8% salt, and olmesartan (1 mg kg(-1)), valsartan (3 mg kg(-1)) or placebo were administered daily until a survival rate of 60% was reached. In the experiment using SHR-SP, the reduction of acetylcholine-induced vascular relaxation and the increase of p22(phox) expression in the placebo-treated group were significantly attenuated by olmesartan and valsartan, but this attenuation was significantly greater for olmesartan. In immunohistological analysis, all areas positive for angiotensin II, p22(phox) and 4-hydroxy-2-nonenal were significantly reduced by olmesartan and valsartan, but again this reduction was significantly greater for olmesartan. In salt-loaded SHR-SP, the number of days to reach a 60% survival rate was 25 and 42 in placebo and valsartan-treated rats, respectively, and this represented a significant difference. The survival rate in olmesartan-treated rats was 95% at day 42, when valsartan-treated rats reached 60% survival, and this difference was also significant. In the surviving rats, olmesartan, but not valsartan, augmented acetylcholine-induced vascular relaxation and attenuated vascular p22(phox) expression. Thus, heterogeneity in binding affinity to AT(1) receptors among ARBs may result in different degrees of vascular protection and lifespan extension.

Authors+Show Affiliations

Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki City, Osaka, Japan. pha010@art.osaka-med.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19662023

Citation

Takai, Shinji, et al. "Significance of Angiotensin II Receptor Blockers With High Affinity to Angiotensin II Type 1 Receptors for Vascular Protection in Rats." Hypertension Research : Official Journal of the Japanese Society of Hypertension, vol. 32, no. 10, 2009, pp. 853-60.
Takai S, Jin D, Ikeda H, et al. Significance of angiotensin II receptor blockers with high affinity to angiotensin II type 1 receptors for vascular protection in rats. Hypertens Res. 2009;32(10):853-60.
Takai, S., Jin, D., Ikeda, H., Sakonjo, H., & Miyazaki, M. (2009). Significance of angiotensin II receptor blockers with high affinity to angiotensin II type 1 receptors for vascular protection in rats. Hypertension Research : Official Journal of the Japanese Society of Hypertension, 32(10), 853-60. https://doi.org/10.1038/hr.2009.116
Takai S, et al. Significance of Angiotensin II Receptor Blockers With High Affinity to Angiotensin II Type 1 Receptors for Vascular Protection in Rats. Hypertens Res. 2009;32(10):853-60. PubMed PMID: 19662023.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Significance of angiotensin II receptor blockers with high affinity to angiotensin II type 1 receptors for vascular protection in rats. AU - Takai,Shinji, AU - Jin,Denan, AU - Ikeda,Hironobu, AU - Sakonjo,Hiroshi, AU - Miyazaki,Mizuo, Y1 - 2009/08/07/ PY - 2009/8/8/entrez PY - 2009/8/8/pubmed PY - 2009/12/31/medline SP - 853 EP - 60 JF - Hypertension research : official journal of the Japanese Society of Hypertension JO - Hypertens Res VL - 32 IS - 10 N2 - Angiotensin II receptor blockers (ARBs) vary in their binding affinities to angiotensin II type 1 (AT(1)) receptors in in vitro experiments. We compared a high-affinity ARB, olmesartan, and a low-affinity ARB, valsartan, in terms of their vascular protective effects in stroke-prone spontaneously hypertensive rats (SHR-SP). Blood pressure was equally reduced by placebo, olmesartan (1 mg kg(-1)) and valsartan (3 mg kg(-1)) daily for 2 weeks. In another experiment, 12-week-old SHR-SP were fed 8% salt, and olmesartan (1 mg kg(-1)), valsartan (3 mg kg(-1)) or placebo were administered daily until a survival rate of 60% was reached. In the experiment using SHR-SP, the reduction of acetylcholine-induced vascular relaxation and the increase of p22(phox) expression in the placebo-treated group were significantly attenuated by olmesartan and valsartan, but this attenuation was significantly greater for olmesartan. In immunohistological analysis, all areas positive for angiotensin II, p22(phox) and 4-hydroxy-2-nonenal were significantly reduced by olmesartan and valsartan, but again this reduction was significantly greater for olmesartan. In salt-loaded SHR-SP, the number of days to reach a 60% survival rate was 25 and 42 in placebo and valsartan-treated rats, respectively, and this represented a significant difference. The survival rate in olmesartan-treated rats was 95% at day 42, when valsartan-treated rats reached 60% survival, and this difference was also significant. In the surviving rats, olmesartan, but not valsartan, augmented acetylcholine-induced vascular relaxation and attenuated vascular p22(phox) expression. Thus, heterogeneity in binding affinity to AT(1) receptors among ARBs may result in different degrees of vascular protection and lifespan extension. SN - 1348-4214 UR - https://www.unboundmedicine.com/medline/citation/19662023/Significance_of_angiotensin_II_receptor_blockers_with_high_affinity_to_angiotensin_II_type_1_receptors_for_vascular_protection_in_rats_ L2 - https://medlineplus.gov/vasculardiseases.html DB - PRIME DP - Unbound Medicine ER -