Angiotensin-Converting Enzyme Inhibitor Prevents Plasminogen Activator Inhibitor-1 Expression in a Rat Model with Cardiovascular Remodeling Induced by Chronic Inhibition of Nitric Oxide Synthesis

Katoh, Makoto; Egashira, Kensuke; Mitsui, Takashi; Chishima, Susumu; Takeshita, Akira; Narita, Hiroshi

doi:10.1006/jmcc.1999.1053

Cited by 74 publications

(54 citation statements)

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“…Indeed, it was recently shown that arterial PAI-1 expression increases 4-fold in L-NAME-treated rats, which can be prevented by ACE inhibition. 10 The present study confirms and extends this observation that long-term L-NAME treatment increases cardiac PAI-1 mRNA expression and suggests that L-NAME-induced PAI-1 expression may be involved in coronary vascular structural changes. The mechanistic link between PAI-1 and the structural and functional cardiovascular changes induced by long-term NOS inhibition, however, has not previously been appreciated.…”

Section: Discussionsupporting

confidence: 88%

“…Thus, long-term treatment with L-NAME not only leads to increased matrix deposition through a variety of mechanisms, including induction of type I collagen production, 8 but also coincidently impairs matrix degradation and turnover by inducing PAI-1. 10 In the present study, L-NAME-induced coronary arterial perivascular fibrosis was abolished in PAI-1 Ϫ/Ϫ mice, indicating that PAI-1 deficiency alone is sufficient to prevent the vascular fibrotic response and to preserve vascular compliance.…”

Section: Discussionsupporting

confidence: 60%

“…9 It was recently reported that long-term NOS inhibition induced vascular PAI-1 expression in rat models. 10 PAI-1, a member of the serpin superfamily of serine protease inhibitors, serves as the primary physiological inhibitor of plasminogen activation. 11 In plasma, PAI-1 is a critical determinant of endogenous fibrinolytic activity and resistance to thrombolysis.…”

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confidence: 99%

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Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition

et al. 2001

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Background-Long-term inhibition of nitric oxide synthase (NOS) is known to induce hypertension and perivascular fibrosis. Recent evidence also suggests that long-term NOS inhibition induces expression of plasminogen activator inhibitor-1 (PAI-1) in vascular tissues and that PAI-1 may contribute to the development of fibrosis after chemical or ionizing injury. On the basis of these observations, we hypothesized that PAI-1 may influence the vascular response to long-term NOS inhibition by N -nitro-L-arginine methyl ester (L-NAME). Methods and Results-We compared the temporal changes in systolic blood pressure and coronary perivascular fibrosis in PAI-1-deficient (PAI-1 Ϫ/Ϫ ) and wild-type (WT) male mice (Nϭ6 per group). At baseline, there were no significant differences in blood pressure between groups. After initiation of L-NAME, systolic blood pressure increased in both groups at 2 weeks. Over an 8-week study period, systolic blood pressure increased to 141Ϯ3 mm Hg in WT animals versus 112Ϯ4 mm Hg in PAI-1 Ϫ/Ϫ mice (PϽ0.0001). The extent of coronary perivascular fibrosis increased significantly in L-NAME-treated WT mice (PϽ0.01 versus PAI-1 Ϫ/Ϫ mice). Cardiac type I collagen mRNA expression was greater in control (PϽ0.01) and L-NAME-treated PAI-1 Ϫ/Ϫ (PϽ0.05) groups than in control WT mice, indicating that PAI-1 deficiency prevents the increase of collagen deposition by promoting matrix degradation. Conclusions-These findings suggest that PAI-1 deficiency alone is sufficient to protect against the structural vascular changes that accompany hypertension in the setting of long-term NOS inhibition. Direct inhibition of vascular PAI-1 activity may provide a new therapeutic strategy for the prevention of arteriosclerotic cardiovascular disease.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 60%

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confidence: 99%

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Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition

et al. 2001

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“…Recently, we and others have reported that chronic inhibition of NO synthesis by administration of N G -nitro-L-arginine methyl ester (L-NAME) induces early inflammation [monocyte infiltration, monocyte chemoattractant protein-1 (MCP-1) expression, and nuclear factor (NF)-B activation] and late cardiovascular remodeling through increases in angiotensin-converting enzyme (ACE) and angiotensin II activities in rats (14-16, 26, 28, 30). Although angiotensin II is not a direct platelet agonist, it is known that angiotensin II may increase arterial thrombogenesis by activation of coagulation factors such as tissue factor (TF) (4,21) or by inhibition of fibrinolytic factors via activation of plasminogen activator inhibitor-1 (PAI-1) or inhibition of plasminogen activator (13,21,31) via angiotensin II type 1 receptor stimulation. We have reported that ACE inhibition with imidapril prevented gene expression, protein production, and activity of PAI-1 in this model (13).…”

mentioning

confidence: 99%

“…Although angiotensin II is not a direct platelet agonist, it is known that angiotensin II may increase arterial thrombogenesis by activation of coagulation factors such as tissue factor (TF) (4,21) or by inhibition of fibrinolytic factors via activation of plasminogen activator inhibitor-1 (PAI-1) or inhibition of plasminogen activator (13,21,31) via angiotensin II type 1 receptor stimulation. We have reported that ACE inhibition with imidapril prevented gene expression, protein production, and activity of PAI-1 in this model (13). However, it is unclear whether arterial thrombogenicity is increased through angiotensin II activity in the rat model of chronic inhibition of NO synthesis.…”

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Long-term inhibition of nitric oxide synthesis increases arterial thrombogenecity in rat carotid artery

Kubo-Inoue

Egashira

Usui

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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Kubo-Inoue, Mayuko, Kensuke Egashira, Makoto Usui, Masao Takemoto, Kisho Ohtani, Makoto Katoh, Hiroaki Shimokawa, and Akira Takeshita. Long-term inhibition of nitric oxide synthesis increases arterial thrombogenecity in rat carotid artery. Am J Physiol Heart Circ Physiol 282: H1478-H1484, 2002. First published November 29, 2001 10.1152/ajpheart.00739.2001.-Reduced activity of endothelial nitric oxide (NO) may be involved in thrombus formation on atherosclerotic plaques, a major cause of acute coronary syndrome. However, mechanisms of such increase in arterial thrombogenecity have not been fully understood. We previously reported that long-term inhibition of NO synthesis by administration of N G -nitro-L-arginine methyl ester (L-NAME) causes hypertension and activates vascular tissue angiotensin-converting enzyme (ACE) activity. We used this model to investigate the mechanism by which long-term impairment of NO activity increases arterial thrombogenecity. We observed cyclic flow variations (CFVs), a reliable marker of platelet thrombi, after the production of stenosis of the carotid artery in rats treated with L-NAME for 4 wk. The thrombin antagonist argatroban suppressed the CFVs. The CFVs were detected in rats receiving L-NAME plus hydralazine but not in rats receiving L-NAME plus an ACE inhibitor (imidapril). Treatment with the ACE inhibitor imidapril, but not with hydralazine, prevented L-NAME-induced increases in carotid arterial ACE activity and attenuated tissue factor expression. These results suggest that long-term inhibition of endothelial NO synthesis may increase arterial thrombogenecity at least in part through angiotensin IIinduced induction of tissue factor and the resultant thrombin generation. These data provide a new insight as to how endothelial NO exhibits antithrombogenic properties of the endothelium.thrombosis; angiotensin-converting enzyme; tissue factor; thrombin OCCLUSIVE OR NONOCCLUSIVE thrombus formation on atherosclerotic plaque is believed to be of prime importance in the cause of acute coronary syndrome as well as the progression of atherosclerosis. Such thrombus formation is triggered by endothelial dysfunction, by exposure of plaque components or local mediators in the subendothelial layers to blood components after endothelial disruption (plaque rupture), or by systemic blood factors (17,25). Thus any interventions that may reduce the risk of thrombus formation might be expected to improve patient outcomes. The antithrombotic effects of nitric oxide (NO) have been studied mainly in in vitro conditions or in in vivo conditions with acute blockade of NO activity. However, the mechanisms by which long-term impairment of NO activity can increase arterial thrombogenesis are not fully understood.Atherosclerosis has been demonstrated to be associated with endothelial dysfunction, which leads to the abnormal production of NO. Endothelial NO has been shown to regulate vascular tone and to inhibit platelet aggregation, thrombus formation, leukocyte adhesion, and vascular proliferation (3,...

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2022

Evidence‐Based Nephrology

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Angiotensin-Converting Enzyme Inhibitor Prevents Plasminogen Activator Inhibitor-1 Expression in a Rat Model with Cardiovascular Remodeling Induced by Chronic Inhibition of Nitric Oxide Synthesis

Cited by 74 publications

References 40 publications

Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition

Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition

Long-term inhibition of nitric oxide synthesis increases arterial thrombogenecity in rat carotid artery

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