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Cited by 411

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Regulatory Roles for APJ, a Seven-transmembrane Receptor Related to Angiotensin-type 1 Receptor in Blood Pressure in Vivo

Open access
Ishida, Junji, Hashimoto, Tatsuo, Hashimoto, Yasumi, Nishiwaki, Shiro, Iguchi, Taku, Harada, Shuichi, Sugaya, Takeshi, Matsuzaki, Hitomi, Yamamoto, Rie, Shiota, Naotaka, Okunishi, Hideki, Kihara, Minoru, Umemura, Satoshi, Sugiyama, Fumihiro, Yagami, Ken-ichi, Kasuya, Yoshitoshi, Mochizuki, Naoki, Fukamizu, Akiyoshi·2004·Journal of Biological Chemistry

Abstract

APJ is a G-protein-coupled receptor with seven transmembrane domains, and its endogenous ligand, apelin, was identified recently. They are highly expressed in the cardiovascular system, suggesting that APJ is important in the regulation of blood pressure. To investigate the physiological functions of APJ, we have generated mice lacking the gene encoding APJ. The base-line blood pressure of APJ-deficient mice is equivalent to that of wild-type mice in the steady state. The administration of apelin transiently decreased the blood pressure of wild-type mice and a hypertensive model animal, a spontaneously hypertensive rat. On the other hand, this hypotensive response to apelin was abolished in APJ-deficient mice. This apelin-induced response was inhibited by pretreatment with a nitric-oxide synthase inhibitor, and apelin-induced phosphorylation of endothelial nitric-oxide synthase in lung endothelial cells from APJ-deficient mice disappeared. In addition, APJ-deficient mice showed an increased vasopressor response to the most potent vasoconstrictor angiotensin II, and the base-line blood pressure of double mutant mice homozygous for both APJ and angiotensin-type 1a receptor was significantly elevated compared with that of angiotensin-type 1a receptor-deficient mice. These results demonstrate that APJ exerts the hypotensive effect in vivo and plays a counterregulatory role against the pressor action of angiotensin II.

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Metadata

Authors
Ishida, J., Hashimoto, T., Hashimoto, Y., Nishiwaki, S., Iguchi, T., Harada, S., Sugaya, T., Matsuzaki, H., Yamamoto, R., Shiota, N., Okunishi, H., Kihara, M., Umemura, S., Sugiyama, F., Yagami, K.-I., Kasuya, Y., Mochizuki, N., & Fukamizu, A.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-06
Volume
279
Issue
25
Pages
26274-26279
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2117196163
Cited by
411
References
25
FWCI
12.51
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Regulatory Roles for APJ, a Seven-transmembrane Receptor Related to Angiotensin-type 1 Receptor in Blood Pressure in Vivo. https://app.cochat.ai/papers/10.1074/jbc.m404149200
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Ishida, J., Hashimoto, T., Hashimoto, Y., Nishiwaki, S., Iguchi, T., Harada, S., Sugaya, T., Matsuzaki, H., Yamamoto, R., Shiota, N., Okunishi, H., Kihara, M., Umemura, S., Sugiyama, F., Yagami, K.-I., Kasuya, Y., Mochizuki, N., & Fukamizu, A. (2004). Regulatory Roles for APJ, a Seven-transmembrane Receptor Related to Angiotensin-type 1 Receptor in Blood Pressure in Vivo. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m404149200

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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