Nitric Oxide and Molsidomine in the Management of Pulmonary Hypertension in Takayasu's Arteritis

Lee, Sang‐Do; Kim, Dong‐Soon; Shim, Tae-Sun; Lim, Chae‐Man; Koh, Younsuck; Kim, Woo-Sung; Kim, Won-Dong

doi:10.1378/chest.119.1.302

Cited by 19 publications

(12 citation statements)

References 11 publications

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“…In this patient, we observed a decrease in brain natriuretic peptide (BNP) levels and an improvement in 6‐minute walk distance after step‐by‐step initiation of each agent (data not shown). Lee et al reported three TA cases with PH in whom reduced PAP and PVR were observed after nitric‐oxide inhalation. PAH‐specific agents have been used and found to be effective in a limited number of TA patients with PH so far .…”

Section: Discussionmentioning

confidence: 99%

Pulmonary hypertension in Takayasu arteritis

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Pulmonary hypertension in Takayasu arteritis

et al. 2018

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“…Other studies also described protective effects: during ischaemia 138, 139, a decrease in PMN infiltration as well as preservation of endothelial cells was seen with the use of NO donors. In hypertensive models, NO donors decreased blood pressure 87, 140, while NO donors during atherosclerosis reduced lesion formation, endothelial dysfunction, and LDL oxidation 141.…”

Section: Therapeutic Manipulation Of Enos Activitymentioning

confidence: 98%

“…This impaired endothelial‐dependent vasodilation is also seen in humans with hypercholesterolaemia, atherosclerosis, and cardiac failure. In other vascular systems such as the lung, impaired eNOS activity can also lead to deregulation of vascular tone and can result in pulmonary hypertension 86–88.…”

Section: Enos In Diseasementioning

confidence: 99%

Protective role of endothelial nitric oxide synthase

Albrecht¹,

Stegeman²,

Heeringa

et al. 2002

The Journal of Pathology

336

230

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Nitric oxide is a versatile molecule, with its actions ranging from haemodynamic regulation to anti-proliferative effects on vascular smooth muscle cells. Nitric oxide is produced by the nitric oxide synthases, endothelial NOS (eNOS), neural NOS (nNOS), and inducible NOS (iNOS). Constitutively expressed eNOS produces low concentrations of NO, which is necessary for a good endothelial function and integrity. Endothelial derived NO is often seen as a protective agent in a variety of diseases. This review will focus on the potential protective role of eNOS. We will discuss recent data derived from studies in eNOS knockout mice and other experimental models. Furthermore, the role of eNOS in human diseases is described and possible therapeutic intervention strategies will be discussed.

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“…However, the use of inhaled NO is hampered by the need for complicated delivery systems and possible toxic side effects ( Weinberger et al , 2001 ), and NO donors could provide a means of improving NO treatment. Although the effect on pulmonary pressure disappeared after 3 weeks, the NO prodrug molsidomine, which can be administered orally, reduced pulmonary pressure in patients with chronic obstructive pulmonary disease ( Lampert et al , 1991 ), and in three patients with PH, secondary to Takayasu's arteritis, 3 months treatment with molsidomine improved hemodynamic parameters ( Lee et al , 2001 ). Molsidomine also lowered the pulmonary arterial pressure in rats with PH evoked by monocrotaline injection or normobaric hypoxia ( Mathew et al , 1997 ), and reduced pulmonary vascular remodelling and ET‐1 expression ( Blumberg et al , 2001 ), but the effect was less pronounced after long‐term treatment ( Blumberg et al , 2001 ).…”

Section: Introductionmentioning

confidence: 99%

The superoxide dismutase mimetic, tempol, blunts right ventricular hypertrophy in chronic hypoxic rats

Elmedal

Dam

Mulvany

et al. 2004

British J Pharmacology

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1 The purpose of this study was to investigate whether a membrane-permeable superoxide dismutase mimetic, tempol, added either alone or in combination with the nitric oxide (NO) donor molsidomine, prevents the development of pulmonary hypertension (PH) in chronic hypoxic rats. 2 Chronic hypobaric hypoxia (10% oxygen) for 2 weeks increased the right ventricular systolic pressure (RVSP), right ventricle and lung wet weight. Relaxations evoked by acetylcholine (ACh) and the molsidomine metabolite SIN-1 were impaired in isolated proximal, but not distal pulmonary arteries, from chronic hypoxic rats. 3 Treatment with tempol (86 mg kg À1 day À1 in drinking water) normalized RVSP and reduced right ventricular hypertrophy, while systemic blood pressure, lung and liver weights, and blunted ACh relaxation of pulmonary arteries were unchanged. 4 Treatment with molsidomine (15 mg kg À1 day À1 in drinking water) had the same effects as tempol, except that liver weight was reduced, and potassium and U46619-evoked vasoconstrictions in pulmonary arteries were increased. Combining tempol and molsidomine did not have additional effects compared to tempol alone. ACh relaxation in pulmonary arteries was not normalized by these treatments. 5 The media to lumen diameter ratio of the pulmonary arteries was greater for the hypoxic rats compared to the normoxic rats, and was not reversed by treatment with tempol, molsidomine, or the combination of tempol and molsidomine. 6 We conclude that tempol, like molsidomine, is able to correct RVSP and reduce right ventricular weight in the rat hypoxic model. Functional and structural properties of pulmonary small arteries were little affected. The results support the possibility that superoxide dismutase mimetics may be a useful means for the treatment of PH.

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Nitric Oxide and Molsidomine in the Management of Pulmonary Hypertension in Takayasu's Arteritis

Cited by 19 publications

References 11 publications

Pulmonary hypertension in Takayasu arteritis

Pulmonary hypertension in Takayasu arteritis

Protective role of endothelial nitric oxide synthase

The superoxide dismutase mimetic, tempol, blunts right ventricular hypertrophy in chronic hypoxic rats

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