scholarly journals Design, synthesis and evaluation of novel angiotensin II receptor 1 antagonists with antihypertensive activities

RSC Advances ◽  
2017 ◽  
Vol 7 (42) ◽  
pp. 26401-26410 ◽  
Author(s):  
Xiao-Lu Bao ◽  
Wei-Bo Zhu ◽  
Tian-Li Shan ◽  
Zhuo Wu ◽  
Rui-Jing Zhang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Antihypertensive Drug ◽  
Drug Candidate ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Design Synthesis ◽  
Long Acting

A novel Ang II receptor 1 antagonist 1f was found to be an efficient, long-acting and safe antihypertensive drug candidate.

scholarly journals Molecular targeting therapy with angiotensin II receptor blocker for prostatic cancer

2011 ◽  
pp. 3-13
Author(s):  
Hiroji Uemura ◽  
Hitoshi Ishiguro ◽  
Yoshinobu Kubota
Keyword(s):  
Prostate Cancer ◽  
Angiotensin Ii ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Angiotensin Ii Receptor Blocker ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Targeting Therapy ◽  
Receptor Blockers ◽  
Prostatic Diseases

Angiotensin II (Ang-II) plays a key role as a vasoconstrictor in controlling blood pressure and electrolyte/fluid homeostasis. Recently it has also been shown that this peptide is a cytokine, acting as a growth factor in cardiovascular and stromal cells. In addition, the physiological function of Ang-II seems to be similar in prostate cancer and stromal cells. It is widely assumed that Ang-II facilitates the growth of both cells, and its receptor blockers (ARBs) have the potential to inhibit the growth of various cancer cells and tumors through the Ang-II receptor type 1 (AT1 receptor). The mechanism of cell growth inhibition by ARBs has been considered to be that of suppression of the signal transduction systems activated by growth factors or cytokines in prostate cancer cells, and suppression of angiogenesis. This review highlights the possible use of ARBs as novel agents for prostatic diseases including prostate cancer and benign hypertrophy, and covers related literature.

Embryonic lethality in Dear gene-deficient mice: new player in angiogenesis

2005 ◽  
Vol 23 (3) ◽  
pp. 257-268 ◽  
Author(s):  
Victoria L. M. Herrera ◽  
Lorenz R. B. Ponce ◽  
Pia D. Bagamasbad ◽  
Benjamin D. VanPelt ◽  
Tamara Didishvili ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Embryonic Lethality ◽  
Female Rats ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Angiotensin Ii Receptor ◽  
Endothelin 1 ◽  
Receptor Isoforms ◽  
Age Range ◽  
Deficient Mice

The dual endothelin-1/angiotensin II receptor (Dear) binds endothelin-1 (ET-1) and angiotensin II (ANG II) with equal affinities in the Dahl S/JRHS rat strain. To elucidate its physiological significance within the context of multiple receptor isoforms and diverse ET-1 and ANG II functions spanning blood pressure regulation, tumor proliferation, and angiogenesis, we characterized mouse Dear and Dear-deficient mice. Unlike null mutant models of ET-1, ANG II, and all other ET-1 and ANG II receptors, Dear−/− deficiency results in impaired angiogenesis, dysregulated neuroepithelial development, and embryonic lethality by embryonic day 12.5. Interestingly, mouse Dear does not bind ANG II, similar to Dahl R/JRHS rat Dear, but binds ET-1 and vascular endothelial growth factor (VEGF) signal peptide (VEGFsp) with equal affinities, suggesting a putative novel multifunction for VEGFsp and a parsimonious mechanism for coordination of VEGF-induced and Dear-mediated pathways. Consistent with its developmental angiogenic role, Dear inhibition results in decreased tumor growth in B16-F10 melanoma cell-induced subcutaneous tumor in female Dear+/−/C57BL6BC10 mice, but not in males (age 3.5 mo), and in 127Cs radiation-induced orthotopic mammary tumors in Sprague-Dawley female rats (age range 3–6.5 mo). Altogether, the data identify Dear as a new player in angiogenesis during development downstream to, and nonredundant with, VEGF-mediated pathways, as well as a putative modulator of tumor angiogenesis acting within a gender-specific paradigm.

Design, synthesis, and evaluation of novelly substituted benzimidazole compounds as angiotensin II receptor antagonists

2005 ◽  
Vol 15 (17) ◽  
pp. 3962-3965 ◽  
Author(s):  
Alka Bali ◽  
Yogita Bansal ◽  
M. Sugumaran ◽  
Jatinder Singh Saggu ◽  
P. Balakumar ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Ii Receptor Antagonists ◽  
Receptor Antagonists ◽  
Design Synthesis

Angiotensin II-receptor stimulation of cytosolic calcium concentration in cultured renal resistance arterioles

1996 ◽  
Vol 271 (6) ◽  
pp. F1239-F1247 ◽  
Author(s):  
Z. Zhu ◽  
W. J. Arendshorst
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Calcium Concentration ◽  
Morphological Properties ◽  
Free Calcium ◽  
Functional Coupling ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Angiotensin Ii Receptor

This study provides an initial characterization of basic morphological properties of cultures of vascular smooth muscle cells (VSMC) from rat preglomerular resistance vessels and of the functional coupling of angiotensin II (ANG II) receptors to cytosolic free calcium concentration ([Ca2+]i (fura 2 fluorescence photometry). Renal VSMC were isolated from interlobular arteries and afferent arterioles (< 50 microns) using an iron oxide sieving method and compared with rat aortic VSMC cultured under similar conditions. Quiescent monolayers maintained uniform morphology and [Ca2+]i signaling profile between passages 3 and 10. Arteriolar and aortic VSMC were spindle shaped and expressed smooth muscle-specific alpha-actin and myosin heavy chains SM-1 and SM-2. ANG II caused a rapid increase in [Ca2+]i, followed by a sustained plateau phase at 50-60% of the peak value. The initial maximum [Ca2+]i responses were dose dependent and of similar magnitude in renal arteriolar and aortic VSMC. ANG II (10(-7) M) increased [Ca2+]i from 50 to 240 nM in arteriolar and from 57 to 201 nM in aortic VSMC (P < 0.001 for both). Inhibition of ANG II effects on [Ca2+]i revealed significant signaling through distinct AT-receptor subtypes (losartan and PD-123319 sensitive) in renal arteriolar VSMC. In contrast, only losartan was effective in aortic VSMC. The AT2-receptor ligand CGP-42112 had no effect in either vessel type. Our results demonstrate that cultured arteriolar VSMC have anatomical similarities to aortic VSMC and functional differences in AT-receptor signaling in response to ANG II. This novel preparation should provide a useful approach with which to investigate cellular mechanisms concerning receptor coupling to signaling pathways involved in vascular reactivity of arteriolar VSMC in the microcirculation in general and the kidney in particular.

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