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    Diverse effects of calcium channel blockers in the collar model
    (Acta Cardiologica, 2005) Kerry, Z; Yasa, M; Sevin, G; Reel, B; Anacak, GY; Ozer, A
    Objective - Calcium channel blockers (CCBs) are among the most frequently prescribed cardiovascular drugs. It has been shown that these drugs have antiatherosclerotic effects in both experimental and clinical settings. However, calcium channel blockers have markedly different chemical structures and different effects on the cardiovascular system.We investigated the effect of CD-832, a Ca+2 channel antagonist, on collar-induced intimal thickening, as well as accompanied reactivity changes in rabbit carotid artery. Methods and results - Rabbits received 5 mg/kg/day CD-832 or vehicle (polyethylene glycol, 0.5 ml/kg/day) intramuscularly for a week before and 2 weeks after the collar application. Histological and isometric force measurements were performed in segments from sham and collared carotid arteries. A three-week treatment with CD-832 did not inhibit the intimal thickening caused by perivascular application of a silicone collar. Potassium chloride (KCI), phenylephrine, 5-hydroxytryptamine (5-HT, serotonin) and histamine induced concentration-dependent contractions in both sham-operated (sham) and collared arteries. Collar-induced attenuations in maximum KCI, histamine, phenylephrine and 5-HT contractions were not affected by CD-832. Collaring caused an increase in pD(2) values of 5-HT and a decrease in those of phenylephrine, histamine and acetylcholine. CD-832 did not affect the altered sensitivity to these agonists. Conclusions -These results demonstrate that, in rabbit carotid artery, CD-832 did not inhibit the collar-induced intimal thickening and did not affect the accompanying changes in vascular reactivity.
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    Effects of treatment with FK409, a nitric oxide donor, on collar-induced intimal thickening and vascular reactivity
    (Elsevier Science Bv, 1999) Yasa, M; Kerry, Z; Yetik, G; Sevin, G; Reel, B; Ozdemir, N; Erhan, Y; Ustunes, L; Berkan, T; Ozer, A
    Intimal thickening in arteries is considered a site of predilection for atherosclerosis. In a rabbit model of early atherosclerosis, a silastic collar was placed around the carotid artery, which resulted in the formation of intimal thickening. We investigated whether the oral application of FK409 ((+)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide, 10 mg kg(-1) day(-1), p.o.), a nitric oxide donor, inhibited the collar-induced intimal thickening as well as accompanying reactivity changes in rabbit carotid artery. The intimal thickening was significantly inhibited by FK409. The collar treatment increased the pD(2) value of 5-hydroxytryptamine (5-HT) whereas it decreased those of phenylephrine and acetylcholine and did not significantly alter that of nitroglycerine. Maximal contractile force development in response to potassium chloride (KCl), 5-HT and phenylephrine was decreased in collared arteries. The collar did not alter the maximal relaxant effects of acetylcholine and nitroglycerine. Despite the significant reduction of intimal thickening, FK409 treatment did not affect these collar-induced modifications in vascular reactivity. (C) 1999 Elsevier Science B.V. All rights reserved.
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    The role of endothelia receptor antagonism in collar-induced intimal thickening and vascular reactivity changes in rabbits
    (Wiley, 2005) Reel, B; Ozkal, S; Islekel, H; Ozer, E; Oktay, G; Sozer, GO; Tanriverdi, S; Turkseven, S; Kerry, Z
    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. Endothelia is known to act as a strong mitogen and to stimulate smooth muscle cell proliferation and migration. We investigated the contribution of endothelia to the development of collar-induced intimal thickening and the effects of TAK-044, (5mg kg(-1) daily, s.c.), a non-selective ETA/ETB receptor antagonist, on intimal thickening and vascular reactivity changes in the collared rabbit carotid artery. Endothelia 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 endothelia 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 endothelia may be involved in the pathogenesis of collar-induced intimal thickening. As an endothelia receptor antagonist, TAK-044 may potentially be beneficial in the treatment of atherosclerosis.