Single injection of a sustained-release prostacyclin analog improves pulmonary hypertension in rats.

Single injection of a sustained-release prostacyclin analog improves pulmonary hypertension in rats. Research Abstract Details 

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Single injection of a sustained-release prostacyclin analog improves pulmonary hypertension in rats. Abstract Text:

Hiroaki Obata,Yoshiki Sakai,Shunsuke Ohnishi,Satoshi Takeshita,Hidezo Mori,Makoto Kodama,Kenji Kangawa,Yoshifusa Aizawa,Noritoshi Nagaya,Hiroaki Obata,Yoshiki Sakai,Shunsuke Ohnishi,Satoshi Takeshita,Hidezo Mori,Makoto Kodama,Kenji Kangawa,Yoshifusa Aizawa,Noritoshi Nagaya,

RATIONALE: Although prostacyclin is recognized as a therapeutic breakthrough for pulmonary hypertension, it needs continuous infusion because of its short action. Therefore, we developed a new drug delivery system for prostacyclin. We prepared ONO-1301MS, a novel sustained-release prostacyclin analog polymerized with poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres. OBJECTIVES: We examined whether ONO-1301MS attenuates monocrotaline (MCT)-induced pulmonary hypertension in rats, and attempted to elucidate the underlying mechanisms responsible for the beneficial effects of ONO-1301MS. METHODS: After MCT injection, rats were randomized to receive a single subcutaneous injection of 100 mg/kg ONO-1301MS or vehicle. MEASUREMENTS AND MAIN RESULTS: We prepared ONO-1301MS, which was polymerized with PLGA to release ONO-1301 for 3 weeks. A single administration of ONO-1301MS achieved sustained elevation of its circulating level and plasma cyclic adenosine 3',5'-monophosphate level for 3 weeks, and attenuated an increase in a metabolite of thromboxane A(2) level. Rats had developed pulmonary hypertension 3 weeks after MCT injection; however, treatment with ONO-1301MS significantly attenuated the increases in right ventricular systolic pressure and right ventricular weight to body weight ratio. ONO-1301MS significantly inhibited hypertrophy of pulmonary arteries. Phosphorylation of extracellular signal-regulated protein kinase (ERK) in the lung was significantly increased in the control group, whereas this increase was markedly attenuated by treatment. CONCLUSIONS: We developed a new drug delivery system for prostacyclin using PLGA and ONO-1301. A single injection of ONO-1301MS resulted in sustained activity for 3 weeks, and attenuated pulmonary hypertension, partly through its antiproliferative effect on vascular smooth muscle cells via inhibition of ERK phosphorylation.

Single injection of a sustained-release prostacyclin analog improves pulmonary hypertension in rats. Publishing Authors By Initials

H Obata,Y Sakai,S Ohnishi,S Takeshita,H Mori,M Kodama,K Kangawa,Y Aizawa,N Nagaya,H Obata,Y Sakai,S Ohnishi,S Takeshita,H Mori,M Kodama,K Kangawa,Y Aizawa,N Nagaya,

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Single injection of a sustained-release prostacyclin analog improves pulmonary hypertension in rats. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: American journal of respiratory and critical care

VOLUME: 177

Page Numbers: 195-201

Journal Abbreviation: Am. J. Respir. Crit. Care Med.

ISSN: 1535-4970

DAY: 1

MONTH: 11

YEAR: 2007

Single injection of a sustained-release prostacyclin analog improves pulmonary hypertension in rats. Information

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LANGUAGE: eng

NlmUniqueID: 9421642

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AFFILIATION: Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.

Country: United States

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MEDLINETA: Am J Respir Crit Care Med

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