Identification of angiotensin II receptor subtypes

Chiu, Andrew T.; Herblin, William F.; McCall, Dale E.; Ardecky, Robert; Carini, David J.; Duncia, John V.; Pease, Lori J.; Wong, Pancras C.; Wexler, Ruth R.; Johnson, Alexander L.; Timmermans, Pieter B.M.W.M.

doi:10.1016/0006-291x(89)91054-1

Cited by 785 publications

(271 citation statements)

References 20 publications

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“…Indeed, the biological active component of RAS, Angiotensin II (Ang II), stimulates endothelial and smooth muscle cells (SMC) proliferation in vitro (Stoll et al, 1995), increases vessel density in rat cremaster muscle (Munzenmaier and Greene, 1996) in the chorioallantoic membrane of the chick embryo (Le Noble et al, 1993), and activates in vivo angiogenesis in the rat subcutaneous sponge granuloma (Walsh et al, 1997). Ang II acts by at least two Ang II receptor subtypes, AT1 and AT2 (Chiu et al, 1989;Timmermans et al, 1993;Whitebread et al, 1989). AT1 receptor has been shown to mediate growth stimulating function of Ang II, whereas AT2 seems to promote growth inhibition (Nakajima et al, 1995;Prescott et al, 1991;Stoll et al, 1995;Walsh et al, 1997).…”

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confidence: 99%

Angiotensin II Angiogenic Effect In Vivo Involves Vascular Endothelial Growth Factor- and Inflammation-Related Pathways

Tamarat

Silvestre

Durie

et al. 2002

Laboratory Investigation

207

161

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SUMMARY:Although accumulating lines of evidence indicate the proangiogenic role of angiotensin II (Ang II), little is known about the molecular mechanisms associated with such an effect. This study aimed to identify molecular events involved in Ang II-induced angiogenesis in the Matrigel model in mice. C57Bl/6 female mice received a subcutaneous injection of either Matrigel or Matrigel with Ang II (10 Ϫ7 M) alone, with Ang II and an AT1 receptor antagonist (candesartan, 10 Ϫ6 M), or with Ang II and AT2 receptor antagonist (PD123319, 10 Ϫ6 M). After 14 days, angiogenesis was assessed in the Matrigel-plug by histological evaluation and cellular counting. Ang II increased by 1.9-fold the number of cells within the Matrigel (p Ͻ 0.01 versus control). Immunohistological analysis revealed the presence of macrophages, endothelial and smooth muscle cells, and the development of vascular-like structure. Such an angiogenic effect was associated with an increase in vascular endothelial growth factor (VEGF) (1.5-fold, p Ͻ 0.01), endothelial nitric oxide (eNOS) (1.7-fold, p Ͻ 0.01), and cyclooxygenase-2 (1.4-fold, p Ͻ 0.05) protein levels measured by Western blotting. Conversely, Ang II treatment did not affect MMP-9 and MMP-2 activity, assessed by zymography. Blockade of AT1 receptor completely prevented the Ang II-induced angiogenesis and protein regulations, whereas that of AT2 was ineffective. Administration of VEGF neutralizing antibody (2.5 g ip twice a week) and cyclooxygenase-2 selective inhibitor (nimesulide, 30 mg/L) also hampered Ang II proangiogenic effect. In addition, Ang II-induced cell ingrowth was impaired by treatment with nitric oxide synthase inhibitor (L-NAME, 10 mg/kg/day) and in eNOS-deficient mice. Therefore, in an in vivo model, Ang II induced angiogenesis through AT1 receptor, which involved activation of VEGF/eNOS-related pathway and of the inflammatory process. (Lab Invest 2002, 82:747-756).

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confidence: 99%

Angiotensin II Angiogenic Effect In Vivo Involves Vascular Endothelial Growth Factor- and Inflammation-Related Pathways

Tamarat

Silvestre

Durie

et al. 2002

Laboratory Investigation

207

161

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“…Saralasin, by contrast, was active in both assays. Andrew Chiu and other members of the DuPont group therefore concluded that two distinct subtypes of angiotensin II receptors exist, subsequently named AT 1 (inhibited by losartan) and AT 2 (inhibited by PD123177 and CGP42112) (Chiu, Herblin, McCall et al 1989). The research group at CibaGeigy independently drew the same conclusions from similar studies with receptor antagonists (Whitebread, Mele, Kamber et al 1989).…”

Section: Characterizing a Functional Receptormentioning

confidence: 90%

Integrating research and development: the emergence of rational drug design in the pharmaceutical industry

Adam

2005

Studies in History and Philosophy of Science Part C: Studies in

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Appears in Studies in History and Philosophy of Biological and Biomedical Sciences 36 (2005). AbstractRational drug design is a method for developing new pharmaceuticals that typically involves the elucidation of fundamental physiological mechanisms. It thus combines the quest for a scientific understanding of natural phenomena with the design of useful technology and hence integrates epistemic and practical aims of research and development. Case studies of the rational design of the cardiovascular drugs propranolol, captopril and losartan provide insights into characteristics and conditions of this integration. Rational drug design became possible in the 1950s when theoretical knowledge of drug-target interaction and experimental drug testing could interlock in cycles of mutual advancement. The integration does not, however, diminish the importance of basic research for pharmaceutical development. Rather, it can be shown that still in the 1990s, linear processes of innovation and the close combination of practical and epistemic work were interdependent.

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“…Two subtypes of angiotensin receptors have been identified; AT1 and AT2 using ligand binding studies. The AT1 R, through which are exerted most of the actions of All, is a G protein coupled, spanning seven transmembrane domains (25). The human AT1R gene locus is mapped to chromosome 3q21 and 25 (26).…”

Section: Angiotensin II Type I Receptor (Atir)mentioning

confidence: 99%

Genes of renin angiotensin system and coronary heart disease

Ashavaid

Shalia

Nair

et al. 2000

Indian J Clin Biochem

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Coronary constriction, proliferation of smooth muscle cells and arrhythmia are involved in the pathophysiology of coronary heart disease and its complications such as myocardial infarction and sudden death. All these effects are favoured by high angiotensin II levels. Angiotensin II is the main effector molecule of the renin angiotensin system and it acts through angiotensin II type receptors. Genetically determined differences in the expression of the components of this system could adversely affect angiotensin II concentration and subsequently heart. Consequently each component of this system represents a potential candidate in the etiology of cardiovascular disease. In this article we review the variation of the angiotensin I converting enzyme, angiotensin II type I receptor and angiotensinogen genes and their association with cardiovascular disease.

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Identification of angiotensin II receptor subtypes

Cited by 785 publications

References 20 publications

Angiotensin II Angiogenic Effect In Vivo Involves Vascular Endothelial Growth Factor- and Inflammation-Related Pathways

Angiotensin II Angiogenic Effect In Vivo Involves Vascular Endothelial Growth Factor- and Inflammation-Related Pathways

Integrating research and development: the emergence of rational drug design in the pharmaceutical industry

Genes of renin angiotensin system and coronary heart disease

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