Effect of verapamil on intimal thickening and vascular reactivity in the collared carotid artery of the rabbit

Üstünes, Levent; Yasa, Mukadder; Kerry, Zeliha; Özdemir, Necmettin; Berkan, Tayfun; Erhan, Yı́ldı́z; Özer, Asli

doi:10.1111/j.1476-5381.1996.tb15592.x

Cited by 17 publications

(29 citation statements)

References 50 publications

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“…The increased activities of MMP-2 and MMP-9 in the collared arteries suggest the possible involvement of these 2 gelatinases in the development of intima and/or vascular reactivity alterations of vascular tissue of rabbits in response to collaring. 22,33 Additionally, we observed that, in the placebo group, while the proMMP-2 band was found in both shamoperated and collared arteries, the active MMP-2 band was found only in collared arteries. This observation also suggests the possibility of involvement of MMPs in the collar-induced intimal thickening.…”

Section: Discussionmentioning

confidence: 85%

MMP-2 and MMP-9 Alteration in Response to Collaring in Rabbits: The Effects of Endothelin Receptor Antagonism

Reel

Oktay

Özkal

et al. 2009

J Cardiovasc Pharmacol Ther

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Matrix metalloproteinases (MMPs), and, in particular, gelatinases (MMP-2 and MMP-9), have been implicated in vascular cell proliferation and/or migration, contributing to intimal thickening, an essential stage in the development of atherosclerosis and restenosis following balloon angioplasty. Endothelin, a strong chemoatractant and mitogen, has been shown to promote smooth muscle cell proliferation and migration by activating MMPs via endothelin-A (ETA) receptors. The positioning of a soft silicon collar around the left carotid artery in rabbits results in intimal thickening. In this study, we investigate the possible role of gelatinases and the effect of a nonselective ETA/ETB receptor antagonist, TAK-044 (5 mg/kg body weight/day, subcutaneously [sc]), on these enzymes. Our results demonstrated that both MMP-2 and MMP-9 activities increased in response to collaring in placebo group, while treatment with TAK-044 significantly suppressed both gelatinase activities and proMMP-2 levels, and inhibited intimal thickening in collared arteries. These results suggest that either enhanced MMP expression or endothelin receptor antagonism may be involved in the formation of intimal thickening in this model.

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Section: Discussionmentioning

confidence: 85%

MMP-2 and MMP-9 Alteration in Response to Collaring in Rabbits: The Effects of Endothelin Receptor Antagonism

Reel

Oktay

Özkal

et al. 2009

J Cardiovasc Pharmacol Ther

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“…22 In this study, con sis tent with pre vi o us re sults, col lar pla cing aro und the ca ro tid ar tery did not affect me an ar te ri al pres su re. 27,28 Be si des, ni fe di pine did not al ter res ting blo od pres su re in the pre sent study.…”

Section: -26mentioning

confidence: 84%

Nifedipine Induces Expansive Vascular Remodeling of Carotid Arteries in Rabbit Collar Model

Reel¹,

Ergür²

2011

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : In ti mal thic ke ning is an adap ti ve res pon se to in jury and to sti mu li ac ting on the ves sel wall. Vas cu lar re mo de ling (VR) is de fi ned as the chan ges in the si ze and/or com po si ti on of the vessels in res pon se to dyna mic and trop hic sti mu li. Inap prop ri a te VR plays a cru ci al ro le in lu men loss and pat ho ge ne sis of car di o vas cu lar di se a ses. Cal ci um chan nel bloc kers (CCBs) ha ve be en known to ha ve vascu lar pro tec ti ve ef fects. Ho we ver, the pre ci se mo le cu lar mec ha nisms of the se ef fects ha ve not be en fully elu ci da ted. The aim of this study was to in ves ti ga te the ef fects of ni fe di pi ne on in ti mal thic ke ning and patho lo gi cal VR, and to exa mi ne the ro le of the dis co i din do ma in re cep tors (DDRs), which are col la gen recep tors, in the VR pro cess in the col lar mo del. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : Whi te rab bits we re ran do mi zed in to two gro ups. The gro ups re ce i ved ve hic le or ni fe di pi ne (40 mg/kg/day, p.o.) for three we eks. Af ter seven days, a non-occ lu si ve si li co ne col lar was pla ced aro und the left ca ro tid ar tery. To eva lu a te in ti mal thic ke ning and VR, the in ti mal are a, me di al and lu mi nal pe ri me ters we re me a su red. Furt her mo re, DDR ex pressi ons we re as ses sed im mu no his toc he mi cally. R Re e s su ul lt ts s: : Ni fe di pi ne did not in hi bit in ti mal thic ke ning. The col lar pro vo ked in ward VR. Ne it her col la gen con tent nor DDR ex pres si ons we re af fec ted by the col lar. Ni fe di pi ne cons ti tu ted hyper trop hic out ward ex pan si ve VR by in vol ving lu mi nal and ar te ri al en lar gement. Ho we ver ni fe di pi ne did not chan ge eit her col la gen in gre di ent or DDR ex pres si ons. C Co on nc c l lu u s si i o on n: : Nife di pi ne did not in hi bit in ti mal thic ke ning. Ho we ver, it re sul ted in fa vo rab le ex pan si ve VR wit ho ut chan ging col la gen con tents and DDR ex pres si ons. Thus, ni fe di pi ne may help to ma in ta in lu mi nal pa tency and to pre vent res te no sis af ter bal lo on an gi op lasty.K Ke ey y W Wo or rd ds s: : Cal ci um chan nel bloc kers; dis co i din re cep tor; rab bits; at he rosc le ro sis; vas cu lar pa tency Ö ÖZ ZE ET T A Am ma aç ç: : İnti mal ka lın laş ma ha sa ra ve da mar du va rı nı et ki le yen uya rı la ra kar şı ve ri len adap tif bir cevap tır.Vas kü ler ye ni den mo del len me (VYM) di na mik ve tro fik uya rı lar dan do la yı da mar la rın bü yük lük ve/ve ya bi le şi min de olu şan de ği şik lik ler ola rak ta nım lan mak ta dır. Uy gun suz VYM lü men kay bın da ve kar di yo vas kü ler has ta lık la rın pa to je ne zin de kri tik rol oy nar. Kal si yum ka nal blo kör le ri nin vas kü ler koru yu cu et ki le ri ol du ğu bi lin mek te dir. Bu nun la bir lik te bu et ki le rin ke sin mo le kü ler me ka niz ma la rı tam ola rak ay dın la tıl ma mış tır. Bu ça lış ma nın ama cı ni fe di pi nin in ti mal...

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“…White rabbits (1.5–2 kg) of either sex were divided into 2 groups. The treatment protocol was as described previously (Ustunes et al , 1996). Briefly, the first group received a single administration of lacidipine (5 mg/kg/day, dissolved in 2.5 ml 0.5% aqueous solution of methylcellulose) via a gastric feeding tube.…”

Section: Methodsmentioning

confidence: 99%

“…Subsequently, the left carotid artery was surgically accessed and surrounded by a non-occlusive, flexible silicone collar (Ustunes et al , 1996, Yasa et al , 1999). The collar was 2 cm in length slightly touching the outer surface of the artery on each end.…”

Section: Methodsmentioning

confidence: 99%

“…The intimal thickening is generally accompanied by alterations in vascular reactivity, such as increased sensitivity to 5-hydroxytryptamine (5-HT) and decreased vasodilator responses to agonists (De Meyer et al , 1994, Kerry et al , 2005, Sobey et al , 1991, Ustunes et al , 1996, Yasa et al , 2007). The effect of lacidipine on vascular dysfunction in early atherosclerosis was unclear.…”

Section: Introductionmentioning

confidence: 99%

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Lacidipine has antiatherosclerotic effects independent of its actions on lipid metabolism and blood pressure

Yetik‐Anacak

Üstünes

Dilsiz

et al. 2010

Vascular Pharmacology

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Summary The anti-atherosclerotic effect of lacidipine has been attributed to its actions on cholesterol levels, lipid metabolism or oxidant stress in advanced disease. The purpose of the present experiments was to examine whether lacidipine is protective of intimal thickening and vascular dysfunction in early atherosclerosis in the absence of the hypertension and hypercholesterolemia. A second goal was to determine whether and to what extent MMP-9 and oxidant stress are involved in possible beneficial effects of lacidipine. Lacidipine treatment (5 mg/kg/day, p.o. for 3 weeks) significantly prevented the collar-induced intimal thickening. MMP-9 expressions were increased by collar but not effected by lacidipine treatment. Nitrotyrosine staining, a marker for oxidant stress was not changed neither by collar nor lacidipine treatment in early atherosclerosis. The enhanced sensitivity to serotonine and diminished sensitivity to acetylcholine in collared arteries were restored to normal levels with treatment. These results demonstrate that the lacidipine treatment prevents the collar-induced intimal thickening and accompanying vascular dysfunction in early atherosclerosis without cholesterol loading. These beneficial effects of lacidipine were not associated with changes in either MMP-9 expression or oxidant stress. However, enhanced endothelium dependent relaxations by lacidipine, suggest that vascular protective effects of nitric oxide may be at least partly, responsible from antiatherosclerotic effects of lacidipine

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Effect of verapamil on intimal thickening and vascular reactivity in the collared carotid artery of the rabbit

Cited by 17 publications

References 50 publications

MMP-2 and MMP-9 Alteration in Response to Collaring in Rabbits: The Effects of Endothelin Receptor Antagonism

MMP-2 and MMP-9 Alteration in Response to Collaring in Rabbits: The Effects of Endothelin Receptor Antagonism

Nifedipine Induces Expansive Vascular Remodeling of Carotid Arteries in Rabbit Collar Model

Lacidipine has antiatherosclerotic effects independent of its actions on lipid metabolism and blood pressure

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