Short-term hemodynamic effect of a new oral PGI2 analogue, Beraprost, in primary and secondary pulmonary hypertension

Saji, Tsutomu; Ozawa, Y; Ishikita, Takashi; Matsuura, Hiroyuki; Matsuo, Norio

doi:10.1016/s0002-9149(96)90408-7

Cited by 82 publications

(31 citation statements)

References 10 publications

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“…As intravenous prostacycline could not be obtained in Japan, we used an oral analogue, BS. Though BS has been reported as effective against PPH and PH with congenital cardiac defect, 17 with our patient it had no obvious effect either clinically or hemodynamically.…”

Section: Discussioncontrasting

confidence: 71%

Long-Term Inhalation of Nitric Oxide for a Patient With Primary Pulmonary Hypertension

et al. 1998

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Section: Discussioncontrasting

confidence: 71%

Long-Term Inhalation of Nitric Oxide for a Patient With Primary Pulmonary Hypertension

et al. 1998

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“…Although the causes of this disorder are complicated, abnormal vasoconstriction appears to be a primary factor in the development of PH. 1,2) Although some kinds of vasodilators, such as calcium blockers and prostacyclin, have been used in the treatment of PH, 3,4) they cause several side effects due to systemic vasodilation. Recent studies have demonstrated that nitric oxide inhalation produces selective pulmonary vasodilation without affecting systemic blood pressure in patients with PH.…”

mentioning

confidence: 99%

Acute and Chronic Effects of T-1032, a Novel Selective Phosphodiesterase Type 5 Inhibitor, on Monocrotaline-Induced Pulmonary Hypertension in Rats.

Inoue

Yano

Noto

et al. 2002

Biological & Pharmaceutical Bulletin

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Pulmonary hypertension (PH) is a fatal disease, characterized by the progressive elevation of pulmonary arterial resistance. Although the causes of this disorder are complicated, abnormal vasoconstriction appears to be a primary factor in the development of PH. 1,2) Although some kinds of vasodilators, such as calcium blockers and prostacyclin, have been used in the treatment of PH, 3,4) they cause several side effects due to systemic vasodilation. Recent studies have demonstrated that nitric oxide inhalation produces selective pulmonary vasodilation without affecting systemic blood pressure in patients with PH. 5,6) However, since the safety of nitric oxide inhalation has not been established, 7) its doses have been restricted. Phosphodiesterases (PDEs) are enzymes, which break down cAMP and/or cGMP, and they play a key role in the regulation of intracellular cyclic nucleotide levels. A phosphodiesterase type 5 (PDE5) is classified as cGMP-bind, cGMP-specific phosphodiesterase. 8,9) PDE5 is abundantly expressed in some specific tissues, including the lung and pulmonary artery.10-12) Therefore, the inhibition of PDE5 is considered to produce an increase in cGMP levels in the lung and pulmonary artery. It has been reported that PDE5 inhibitors such as zaprinast, E-4021 and sildenafil preferably dilate the pulmonary artery in vivo and in vitro experimental conditions. [13][14][15][16][17][18] T-1032 (methyl 2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridylmethoxy)-4-(3,4,5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate) is a novel inhibitor of PDE5 (IC 50 ϭ0.001 mM; canine lung). The selectivity for PDE5 over other PDEs in T-1032 is similar to that of sildenafil (IC 50 : PDE1; 3 mM, PDE2; 9.7 mM, PDE3; Ͼ100 mM, PDE4; 3.3 mM).19) T-1032 shows potentiating effects on the nitric oxide/cGMP signaling pathway in isolated rat aorta and rabbit corpus cavernosum. 20) In addition, an intraduodenal administration of T-1032 potentiates the penile tumescence induced by pelvic nerve stimulation, probably through the blockade of PDE5 in anesthetized dogs.21) These results suggest that T-1032 potentiates a nitric oxide/cGMP pathway inhibitor and is orally active compound in animal studies.The acute hemodynamic effects by PDE5 inhibitors on pulmonary circulation have been examined in animal models with PH. 13,15,18) However, only a few studies have reported whether the chronic treatment is effective for improving cardiac remodeling and its related death in an animal model with PH. 22) In this study, we first examined the hemodynamic properties of T-1032 in MCT-induced PH rats, and we next evaluated the chronic effect of T-1032 on cardiac remodeling and its related death in MCT-induced PH rats. MATERIAL AND METHODSThis study was approved by the Animal Research Committee of Tanabe Seiyaku Co., Ltd.Animal Preparation Monocrotaline (MCT, 70 mg/kg) was subcutaneously administered in male Wistar rats weighing 94-107 g, as described previously. 23)Acute Hemodynamic Effects in MCT Rats Twenty-six days after MCT (70 mg/kg) or vehicle...

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“…It has beneficial effects for patients in NYHA-FC I or II, and the effects persist from several to 9 months. 46 BPS reaches peak concentration after 30 min and has an elimination half-life of 35-40 min. 46,47 However, the effect of treatment is not sustained at 9 or 12 months.…”

Section: Pgi2mentioning

confidence: 99%

Update on Pediatric Pulmonary Arterial Hypertension

Saji

2013

Circ J

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Short-term hemodynamic effect of a new oral PGI2 analogue, Beraprost, in primary and secondary pulmonary hypertension

Cited by 82 publications

References 10 publications

Long-Term Inhalation of Nitric Oxide for a Patient With Primary Pulmonary Hypertension

Long-Term Inhalation of Nitric Oxide for a Patient With Primary Pulmonary Hypertension

Acute and Chronic Effects of T-1032, a Novel Selective Phosphodiesterase Type 5 Inhibitor, on Monocrotaline-Induced Pulmonary Hypertension in Rats.

Update on Pediatric Pulmonary Arterial Hypertension

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