Application of Serial In Vivo Magnetic Resonance Imaging to Evaluate the Efficacy of Endothelin Receptor Antagonist SB 217242 in the Rat Carotid Artery Model of Neointima Formation

Chandra, Sudeep; Clark, Lynne V.; Coatney, Robert W.; Phan, Le Ha; Sarkar, Susanta K.; Ohlstein, Eliot H.

doi:10.1161/01.cir.97.22.2252

Cited by 12 publications

(9 citation statements)

References 37 publications

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“…Considering that the role of the endothelin receptor subtypes in the formation of intimal thickening still requires further clarification (Azuma et al 1994), a selective ET A receptor antagonist, ABT 147627, significantly reduced neointimal hyperplasia forming over porcine coronary-stented injuries (McKenna et al 1998). Similarly, SB 217242, a nonpeptide ET A /ET B receptor antagonist, has been shown to attenuate neointima formation in the rat carotid artery balloon angioplasty model (Chandra et al 1998). Although TAK-044 has been accepted as a nonselective ET A /ET B receptor antagonist, receptor-binding experiments revealed that TAK-044 has the characteristics of an ET A -preferring antagonist (Masuda et al 1996).…”

Section: Discussionmentioning

confidence: 99%

The role of endothelin receptor antagonism in collar-induced intimal thickening and vascular reactivity changes in rabbits

Reel

Sozer

Türkseven

et al. 2005

Journal of Pharmacy and Pharmacology

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Intimal thickening, due to smooth muscle cell migration and proliferation, is considered to be one of the major components of vascular proliferative disorders such as atherosclerosis and restenosis. One experimental model, resulting in intimal thickening in the rabbit, involves placing a silicon collar around the carotid artery, and is used in this study. Endothelin is known to act as a strong mitogen and to stimulate smooth muscle cell proliferation and migration. We investigated the contribution of endothelin to the development of collar-induced intimal thickening and the effects of TAK-044, (5 mg kg(-1) daily, s.c.), a non-selective ET(A)/ET(B) receptor antagonist, on intimal thickening and vascular reactivity changes in the collared rabbit carotid artery. Endothelin levels and the intimal cross-sectional area, as well as the ratio of intimal area to media (index), increased significantly in collared arteries as compared with those in sham-operated arteries. TAK-044 significantly inhibited intimal thickening and also decreased the index without affecting increased endothelin levels in collared arteries. Vascular reactivity changes in response to collaring produced predictable effects, such as decreased contractile responses to vasoconstrictor agents and increased sensitivity to serotonin (5-hydroxytryptamine, 5-HT). In terms of contractile responses in this model, TAK-044, in particular, did not affect collar-induced vascular reactivity changes. These results suggest that endothelin may be involved in the pathogenesis of collar-induced intimal thickening. As an endothelin receptor antagonist, TAK-044 may potentially be beneficial in the treatment of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

The role of endothelin receptor antagonism in collar-induced intimal thickening and vascular reactivity changes in rabbits

Reel

Sozer

Türkseven

et al. 2005

Journal of Pharmacy and Pharmacology

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“…MRI also failed to detect lesions induced by a silastic collar around rabbit carotid arteries because of insufficient resolution. 22 Most studies in rats after balloon angioplasty [23][24][25] report changes in lumen volume without direct plaque visualization. Using surgically implanted coils, only Arnder et al 26 and Summers et al 27 detected plaque in vivo in the rat.…”

Section: Discussionmentioning

confidence: 99%

Repeated Three-Dimensional Magnetic Resonance Imaging of Atherosclerosis Development in Innominate Arteries of Low-Density Lipoprotein Receptor-Knockout Mice

et al. 2002

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Background-In vivo methods to evaluate the size and composition of atherosclerotic lesions in animal models of atherosclerosis would assist in the testing of antiatherosclerotic drugs. We have developed an MRI method of detecting atherosclerotic plaque in the major vessels at the base of the heart in low-density lipoprotein (LDL) receptor-knockout (LDLR Ϫ/Ϫ ) mice on a high-fat diet. Methods and Results-Three-dimensional fast spin-echo magnetic resonance images were acquired at 7 T by use of cardiac and respiratory triggering, with Ϸ140-m isotropic resolution, over 30 minutes. Comparison of normal and fat-suppressed images from female LDLR Ϫ/Ϫ mice 1 week before and 8 and 12 weeks after the transfer to a high-fat diet allowed visualization and quantification of plaque development in the innominate artery in vivo. Plaque mean cross-sectional area was significantly greater at week 12 in the LDLR Ϫ/Ϫ mice (0.14Ϯ0.086 mm 2 [meanϮSD]) than in wild-type control mice on a normal diet (0.017Ϯ0.031 mm 2 , PϽ0.01). In the LDLR Ϫ/Ϫ mice, but not control mice, increase in plaque burden at week 12 relative to week 1 was also highly significant (Pϭ0.001). Lumen cross section was not significantly different between time points or groups. MRI and histological assessments of plaque size were closely correlated (Rϭ0.8). The lumen of proximal coronary arteries could also be visualized. Conclusions-This

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“…Ohlstein et al [68] and Chandra et al [69] performed in vivo (at 4.7T) and ex vivo (at 9.4T) carotid artery imaging in rats. In these ex vivo studies, the various layers of the arterial wall were clearly defined.…”

Section: Techniques For Assessing Cardiac Physiologymentioning

confidence: 99%

“…In rats, the common carotid artery is often used to create endothelial injury due to its accessibility and size [100]. Assessment of injury and disease progression in this model have traditionally relied on histopathological analysis with cross-sectional slides [101]; increasingly, standard MRI and MRA techniques as well as the more novel MR microscopy and contrast agents are being used to assess the vessel wall and quantify the degree of restenosis in addition to histology [68, 69, 102, 103]. …”

Section: Experimental Animal Models Of Cardiovascular Diseasementioning

confidence: 99%

Cardiovascular Magnetic Resonance Imaging in Experimental Models

Price¹

2010

TOCMJ

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Cardiovascular magnetic resonance (CMR) imaging is the modality of choice for clinical studies of the heart and vasculature, offering detailed images of both structure and function with high temporal resolution.Small animals are increasingly used for genetic and translational research, in conjunction with models of common pathologies such as myocardial infarction. In all cases, effective methods for characterising a wide range of functional and anatomical parameters are crucial for robust studies.CMR is the gold-standard for the non-invasive examination of these models, although physiological differences, such as rapid heart rate, make this a greater challenge than conventional clinical imaging. However, with the help of specialised magnetic resonance (MR) systems, novel gating strategies and optimised pulse sequences, high-quality images can be obtained in these animals despite their small size. In this review, we provide an overview of the principal CMR techniques for small animals for example cine, angiography and perfusion imaging, which can provide measures such as ejection fraction, vessel anatomy and local blood flow, respectively. In combination with MR contrast agents, regional dysfunction in the heart can also be identified and assessed. We also discuss optimal methods for analysing CMR data, particularly the use of semi-automated tools for parameter measurement to reduce analysis time. Finally, we describe current and emerging methods for imaging the developing heart, aiding characterisation of congenital cardiovascular defects. Advanced small animal CMR now offers an unparalleled range of cardiovascular assessments. Employing these methods should allow new insights into the structural, functional and molecular basis of the cardiovascular system.

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Application of Serial In Vivo Magnetic Resonance Imaging to Evaluate the Efficacy of Endothelin Receptor Antagonist SB 217242 in the Rat Carotid Artery Model of Neointima Formation

Cited by 12 publications

References 37 publications

The role of endothelin receptor antagonism in collar-induced intimal thickening and vascular reactivity changes in rabbits

The role of endothelin receptor antagonism in collar-induced intimal thickening and vascular reactivity changes in rabbits

Repeated Three-Dimensional Magnetic Resonance Imaging of Atherosclerosis Development in Innominate Arteries of Low-Density Lipoprotein Receptor-Knockout Mice

Cardiovascular Magnetic Resonance Imaging in Experimental Models

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