Effect of an angiotensin II receptor antagonist, candesartan cilexetil, on canine intima hyperplasia after balloon injury

Miyazaki, Mizuo; Wada, Takeo; Shiota, Naotaka; Takai, Shinji

doi:10.1038/sj.jhh.1000745

Cited by 52 publications

(55 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8 These findings are important to understanding of the pathogenesis of endothelial dysfunction observed in cardiovascular disease, because vascular Ang II and ACE are increased in atherosclerotic lesions and restenotic lesions after angioplasty. 18,19,[23][24][25] The present study demonstrated a significant decrease in vascular HGF mRNA in porcine coronary balloon-injured artery, consistent with our previous report. 8 This phenomenon provides the interesting hypothesis that disruption of the autocrine-paracrine local HGF system, which maintains endothelial cell growth, by Ang II may result in abnormal growth of VSMC and endothelial dysfunction, given that endothelial cells secrete antiproliferative substances.…”

Section: Discussionsupporting

confidence: 81%

“…Negative regulation of local HGF production, probably by Ang II, may play a physiological role in vascular disease, given the activation of the vascular renin angiotensin system in atherosclerosis, restenosis, and hypertension in humans and in experimental models. 18,19,23,24 Figure 5. Effects of perindopril on vasodilator response to bradykinin 28 days after balloon injury (nϭ5 per group).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of Neointima by Angiotensin-Converting Enzyme Inhibitor in Porcine Coronary Artery Balloon-Injury Model

Matsumoto

Morishita²,

Moriguchi³

et al. 2001

Hypertension

View full text Add to dashboard Cite

Abstract-Because hepatocyte growth factor (HGF) stimulates growth of endothelial cells exclusively without replication of vascular smooth muscle cells, we hypothesized that HGF may play a role in cardiovascular disease. In human vascular smooth muscle cells, angiotensin II suppressed local vascular HGF production in a dose-dependent manner. Using a rat balloon-injury carotid artery model, we demonstrated that blockade of angiotensin II inhibited neointimal formation, accompanied by a significant increase in local HGF production. However, the relation of vascular HGF to endothelial function was not clarified. Moreover, it is important to test the hypothesis in animal models that are more similar to human restenosis. Thus, in the present study, we used a porcine coronary artery balloon-injury model to study the role of angiotensin II in regulation of the local HGF system in vivo. Expression of HGF mRNA was significantly decreased in balloon-injured coronary arteries versus intact vessels. An angiotensin-converting enzyme (ACE) inhibitor (perindopril) significantly inhibited neointimal formation after balloon injury compared with vehicle (PϽ0.05). In addition, vasodilator response of balloon-injured coronary arteries to bradykinin was restored by perindopril treatment, whereas no vasodilator response was observed in balloon-injured vessels treated with vehicle. Vasodilator response of balloon-injured arteries induced by perindopril was completely abolished by N w -nitro-L-arginine methyl ester. Of particular interest, vascular HGF mRNA was significantly increased in balloon-injured vessels treated with perindopril as compared with vehicle. Overall, the present study demonstrated that ACE inhibitor significantly inhibited neointimal formation, accompanied by significant improvement of endothelial dysfunction and a significant increase in local vascular HGF mRNA in vivo in a porcine coronary artery balloon-injury model. Given the strong mitogenic activity of HGF on endothelial cells, improvement of endothelial dysfunction by perindopril might be due to increased local HGF expression through enhancement of reendothelialization after balloon injury, in addition to its direct effect, ACE inhibition. Downregulation of the local vascular HGF system may play an important role in the pathogenesis of cardiovascular disease. From this viewpoint, we previously reported that hepatocyte growth factor (HGF) has the unique characteristic of stimulating endothelial cell growth exclusively without stimulating VSMC growth, 3,4 although HGF is well known to be a mesenchyme-derived pleiotropic factor that regulates cell growth and motility and morphogenesis of various types of cells. 5,6 Moreover, the presence of HGF and its specific receptor, c-met, has been detected in vascular tissues. 7 Our previous reports documented that angiotensin (Ang) II significantly inhibited local HGF production through transforming growth factor (TGF)-␤ activation and a non-TGF-␤ pathway. 8,9 In addition, an angiotensin-converting enzyme (ACE) inhibitor o...

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Inhibition of Neointima by Angiotensin-Converting Enzyme Inhibitor in Porcine Coronary Artery Balloon-Injury Model

Matsumoto

Morishita²,

Moriguchi³

et al. 2001

Hypertension

View full text Add to dashboard Cite

show abstract

“…As might be predicted from this enzyme distribution, candesartan cilexetil significantly suppressed the formation of intimal hyperplasia in both the carotid and femoral arteries, while enalapril significantly suppressed intimal hyperplasia in the femoral but not the carotid arteries. 87 Candesartan cilexetil and enalapril reduced blood pressure almost equally, but enalapril increased plasma renin activity more strongly, and significantly decreased vascular and plasma ACE activities. These results demonstrate that the local production of angiotensin II is involved in the hyperplasia seen in injured intima, and that differences exist in the tissue distribution of the angiotensin II synthetic enzymes, ACE and chymase, which results in a difference in the ability of ACE inhibitors and AIIRAs to prevent hyperplasia in different regions of the vascular system.…”

Section: Pharmacological Properties Of Candesartan Cilexetilmentioning

confidence: 97%

“…Candesartan cilexetil or enalapril were administered to dogs twice daily for 5 weeks. 87 After the first week of active drug therapy, the common carotid and femoral arteries were unilaterally injured by balloon catheterisation. In the common carotid arteries, both ACE and chymase activities increased, with chymase showing the greater increase; in the femoral artery, only ACE was increased by the injury.…”

Section: Pharmacological Properties Of Candesartan Cilexetilmentioning

confidence: 99%

Blocking the tissue renin-angiotensin system: the future cornerstone of therapy

Unger

Azizi

Gg³

2000

J Hum Hypertens

View full text Add to dashboard Cite

The development of angiotensin-converting enzyme inhibitors and selective angiotensin type 1 (AT 1 )-receptor antagonists has provided new insights into understanding the mechanism of the renin-angiotensin system (RAS) in the pathophysiology of cardiovascular disease. There is good evidence from meta-analyses that shows that inhibition of the RAS achieves organ protection features that go beyond blood pressure control. Candesartan cilexetil, a new angiotensin II receptor

show abstract

“…However, in clinic, an AT 1 -receptor antagonist, but not an ACE inhibitor, could prevent restenosis after PTCA (13,14). Dog vascular tissues, like humans, contain ACE and chymase as Ang II-forming enzymes, and an AT 1 -receptor antagonist was effective in preventing vascular proliferation after balloon injury and bypass graft in the dog, but an ACE inhibitor was ineffective (15,16). Such species differences in the effect of ACE inhibitor on the proliferation of vascular tissues may depend on whether or not a given species possesses Ang II-forming chymase in vascular tissue.…”

Section: Introductionmentioning

confidence: 98%

A Single Treatment With a Specific Chymase Inhibitor, TY-51184, Prevents Vascular Proliferation in Canine Grafted Veins

2004

View full text Add to dashboard Cite

Abstract. In this study, we evaluated whether a specific chymase inhibitor, TY-51184 (2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl]oxazole-4-carboxylicacid), prevents the vascular proliferation in canine grafted veins. In the placebo-and chymase inhibitor-treated groups, the external jugular vein was infiltrated with saline and 10 mM TY-51184, respectively, and then it was grafted to the ipsilateral carotid artery. The non-surgical dogs were used as the control group. By 28 days after grafting, the chymase and ACE activities were significantly increased in the injured arteries. TY-51184 significantly reduced the chymase activity in the grafted veins, while it did not affect the ACE activity. The intimal areas in the placebo-and TY-51184-treated groups were 3.32 ± 0.16 and 1.96 ± 0.52 mm 2 , respectively, and this difference was significant. The ratios of intimal area to medial area in the placebo-and TY-51184-treated groups were 66.8 ± 3.5% and 34.9 ± 9.2%, respectively, and this difference was also significant. There was a significant relationship between vascular proliferation and chymase activity, but not ACE activity. In this study, we demonstrated that a single treatment with a specific chymase inhibitor, TY-51184, could prevent the vascular proliferation in canine grafted veins.

show abstract

Effect of an angiotensin II receptor antagonist, candesartan cilexetil, on canine intima hyperplasia after balloon injury

Cited by 52 publications

References 15 publications

Inhibition of Neointima by Angiotensin-Converting Enzyme Inhibitor in Porcine Coronary Artery Balloon-Injury Model

Inhibition of Neointima by Angiotensin-Converting Enzyme Inhibitor in Porcine Coronary Artery Balloon-Injury Model

Blocking the tissue renin-angiotensin system: the future cornerstone of therapy

A Single Treatment With a Specific Chymase Inhibitor, TY-51184, Prevents Vascular Proliferation in Canine Grafted Veins

Contact Info

Product

Resources

About