Tags

Type your tag names separated by a space and hit enter

Effects of olmesartan, an AT1 receptor antagonist, on hypoxia-induced activation of ERK1/2 and pro-inflammatory signals in the mouse lung.
Naunyn Schmiedebergs Arch Pharmacol. 2006 Dec; 374(3):235-48.NS

Abstract

The present study aimed to investigate the effects of olmesartan, an antagonist for angiotensin II receptor type 1(AT1), on the activation of extracellular signal-regulated kinases (ERK)1/2, tissue remodeling, and pro-inflammatory signals in the right ventricle and lung of mice during the early phase of hypobaric hypoxia. Phosphorylation of ERK1/2 in both tissue types in response to hypoxia peaked at 1-3 days, and declined rapidly in the right ventricle, whereas in the lung it was sustained for at least 8 days. Upregulation of angiotensinogen mRNA was observed in the hypoxic lung at 4-9 days, but not in the hypoxic right ventricle and pulmonary artery. Olmesartan inhibited the hypoxia-induced phosphorylation of ERK1/2 in the lung, but not in the right ventricle. Neither right ventricular hypertrophy nor the thickening of the intrapulmonary arterial wall was ameliorated by olmesartan. However, this drug inhibited the expression of the mRNA for angiotensinogen and several pro-inflammatory factors, including interleukin-6 and inducible nitric oxide synthase in the hypoxic lung. These results suggest that olmesartan blocks a potential positive feedback loop of the angiotensin II-AT1 receptor system, which may lead to attenuate pro-inflammatory signals in the mouse lung, that are associated with hypoxic pulmonary hypertension, without inducing any appreciable effects on the compensatory cardiopulmonary hypertrophy at an early phase of exposure to a hypobaric hypoxic environment.

Authors+Show Affiliations

Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka, 422-8526, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17089097

Citation

Tanabe, Yoshiyuki, et al. "Effects of Olmesartan, an AT1 Receptor Antagonist, On Hypoxia-induced Activation of ERK1/2 and Pro-inflammatory Signals in the Mouse Lung." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 374, no. 3, 2006, pp. 235-48.
Tanabe Y, Morikawa Y, Kato T, et al. Effects of olmesartan, an AT1 receptor antagonist, on hypoxia-induced activation of ERK1/2 and pro-inflammatory signals in the mouse lung. Naunyn Schmiedebergs Arch Pharmacol. 2006;374(3):235-48.
Tanabe, Y., Morikawa, Y., Kato, T., Kanai, S., Watakabe, T., Nishijima, A., Iwata, H., Isobe, K., Ishizaki, M., & Nakayama, K. (2006). Effects of olmesartan, an AT1 receptor antagonist, on hypoxia-induced activation of ERK1/2 and pro-inflammatory signals in the mouse lung. Naunyn-Schmiedeberg's Archives of Pharmacology, 374(3), 235-48.
Tanabe Y, et al. Effects of Olmesartan, an AT1 Receptor Antagonist, On Hypoxia-induced Activation of ERK1/2 and Pro-inflammatory Signals in the Mouse Lung. Naunyn Schmiedebergs Arch Pharmacol. 2006;374(3):235-48. PubMed PMID: 17089097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of olmesartan, an AT1 receptor antagonist, on hypoxia-induced activation of ERK1/2 and pro-inflammatory signals in the mouse lung. AU - Tanabe,Yoshiyuki, AU - Morikawa,Yuki, AU - Kato,Takao, AU - Kanai,Satoshi, AU - Watakabe,Taichi, AU - Nishijima,Ami, AU - Iwata,Hijiri, AU - Isobe,Kaori, AU - Ishizaki,Mayumi, AU - Nakayama,Koichi, Y1 - 2006/11/07/ PY - 2006/03/20/received PY - 2006/09/29/accepted PY - 2006/11/8/pubmed PY - 2007/7/31/medline PY - 2006/11/8/entrez SP - 235 EP - 48 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 374 IS - 3 N2 - The present study aimed to investigate the effects of olmesartan, an antagonist for angiotensin II receptor type 1(AT1), on the activation of extracellular signal-regulated kinases (ERK)1/2, tissue remodeling, and pro-inflammatory signals in the right ventricle and lung of mice during the early phase of hypobaric hypoxia. Phosphorylation of ERK1/2 in both tissue types in response to hypoxia peaked at 1-3 days, and declined rapidly in the right ventricle, whereas in the lung it was sustained for at least 8 days. Upregulation of angiotensinogen mRNA was observed in the hypoxic lung at 4-9 days, but not in the hypoxic right ventricle and pulmonary artery. Olmesartan inhibited the hypoxia-induced phosphorylation of ERK1/2 in the lung, but not in the right ventricle. Neither right ventricular hypertrophy nor the thickening of the intrapulmonary arterial wall was ameliorated by olmesartan. However, this drug inhibited the expression of the mRNA for angiotensinogen and several pro-inflammatory factors, including interleukin-6 and inducible nitric oxide synthase in the hypoxic lung. These results suggest that olmesartan blocks a potential positive feedback loop of the angiotensin II-AT1 receptor system, which may lead to attenuate pro-inflammatory signals in the mouse lung, that are associated with hypoxic pulmonary hypertension, without inducing any appreciable effects on the compensatory cardiopulmonary hypertrophy at an early phase of exposure to a hypobaric hypoxic environment. SN - 0028-1298 UR - https://www.unboundmedicine.com/medline/citation/17089097/Effects_of_olmesartan_an_AT1_receptor_antagonist_on_hypoxia_induced_activation_of_ERK1/2_and_pro_inflammatory_signals_in_the_mouse_lung_ L2 - https://dx.doi.org/10.1007/s00210-006-0110-1 DB - PRIME DP - Unbound Medicine ER -