Role of Secretory Phospholipase A<SUB>2</SUB> in Rhythmic Contraction of Pulmonary Arteries of Rats With Monocrotaline-Induced Pulmonary Arterial Hypertension
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概要
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Excessive stretching of the vascular wall in accordance with pulmonary arterial hypertension (PAH) induces a variety of pathogenic cellular events in the pulmonary arteries. We previously reported that indoxam, a selective inhibitor for secretory phospholipase A<SUB>2</SUB> (sPLA<SUB>2</SUB>), blocked the stretch-induced contraction of rabbit pulmonary arteries by inhibition of untransformed prostaglandin H<SUB>2</SUB> (PGH<SUB>2</SUB>) production. The present study was undertaken to investigate involvement of sPLA<SUB>2</SUB> and untransformed PGH<SUB>2</SUB> in the enhanced contractility of pulmonary arteries of experimental PAH in rats. Among all the known isoforms of sPLA<SUB>2</SUB>, sPLA<SUB>2</SUB>-X transcript was most significantly augmented in the pulmonary arteries of rats with monocrotaline-induced pulmonary hypertension (MCT-PHR). The pulmonary arteries of MCT-PHR frequently showed two types of spontaneous contraction in response to stretch; 27% showed rhythmic contraction, which was sensitive to indoxam and SC-560 (selective COX-1 inhibitor), but less sensitive to NS-398 (selective COX-2 inhibitor); and 47% showed sustained incremental tension (tonic contraction), which was insensitive to indoxam and SC-560, but sensitive to NS-398 and was attenuated to 45% of the control. Only the rhythmically contracting pulmonary arteries of MCT-PHR produced a substantial amount of untransformed PGH<SUB>2</SUB>, which was abolished by indoxam. These results suggest that sPLA<SUB>2</SUB>-mediated PGH<SUB>2</SUB> synthesis plays an important role in the rhythmic contraction of pulmonary arteries of MCT-PHR.
著者
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Morikawa Yuki
Department Of Biotechnology Tokyo University Of Agriculture And Technology
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Nakayama Koichi
Department Of Cellular And Molecular Pharmacology Graduate School Of Pharmaceutical Sciences Univers
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Tanabe Yoshiyuki
Department Of Molecular And Cellular Pharmacology School Of Pharmaceutical Sciences Iwate Medical Un
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Kamataki Akihisa
The Department Of Pathology School Of Medicine Iwate Medical University
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Sawai Takashi
The Department Of Pathology School Of Medicine Iwate Medical University
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Sawai Takashi
The Department of Pathology, School of Medicine, Iwate Medical University, Japan
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Saito-Tanji Maki
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Iwate Medical University, Japan
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