Journal of Yeungnam Medical Science
- Volume 23 Issue 1
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- Pages.36-44
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- 2006
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- 2799-8010(eISSN)
Effects of Cyclooxygenase Inhibitors on Vascular Reactivity and Alterations of Cyclooxygenase Expression
혈관 반응성에 대한 Cyclooxygenase 억제제 효과와 Cyclooxygenase 발현 변화
- Lee, Ki-Young (Department of Internal Medicine, Ulsan University Hospital) ;
- Park, Jin-Woo (Department of Internal Medicine, Ulsan University Hospital) ;
- Eum, Eun-A (Department of Internal Medicine, Ulsan University Hospital) ;
- Kang, Young-Jin (Department of Pharmacology, College of Medicine, Yeungnam University) ;
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Lee, Kwang-Youn
(Department of Pharmacology, College of Medicine, Yeungnam University) ;
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Choi, Hyoung-Chul
(Department of Pharmacology, College of Medicine, Yeungnam University)
- 이기영 (울산대학교 병원 내과) ;
- 박진우 (울산대학교 병원 내과) ;
- 엄은아 (울산대학교 병원 내과) ;
- 강영진 (영남대학교 의과대학 약리학교실) ;
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이광윤
(영남대학교 의과대학 약리학교실) ;
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최형철
(영남대학교 의과대학 약리학교실)
- Published : 2006.06.30
Abstract
Background: There is controversy regarding whether COX-2 specific inhibitors are associated with elevation of blood pressure. We compared the effects of aspirin, indomethacin, and celecoxib for vascular reactivity induced by phenylephrine. We also tested the effects of indomethacin and NO donor on COX-1 and COX-2 protein expression, as well as nitrite production in culture medium of vascular smooth muscle cells. Materials and Methods: In this experiment, we used the isometric tension study for vascular reactivity. After 45 minutes of pretreatment with aspirin, indomethacin, celecoxib, and phenylephrine induced contractions were tested. COX-1 and COX-2 protein expressions were analyzed by Western blot and nitrite production by the Griess reaction. Results: Although celecoxib pretreatment caused enhanced arterial contraction, aspirin pretreatment induced more potent arterial contraction than celecoxib in the isometric tension study of rabbit femoral artery. COX-1 protein expression was unchanged by indomethacin, SNP and NOR-3; COX-2 protein expression was increased by the addition of indomethacin, SNP, and NOR-3. Especially, NOR-3, a NO donor, significantly increased COX-2 protein expression with unstimulated conditions as well as LPS stimulation. Induction of nitrite production was higher with NOR-3 treatment than SNP treatment with LPS stimulation. Conclusion: These results suggest that aspirin caused more potent vascular contraction than celecoxib and indomethacin. COX-2 expression in VSMC depended on the types of NO donor and LPS stimulation.
진통과 해열작용을 가진 NSAIDs는 소화기계에 대한 부작용 때문에 COX-2 선택성 억제제로 대체되고 있다. 그러나 COX-2 선택적 억제제는 심혈관계에 대한 부작용이 보고되고 있어 혈관 평활근에 대한 직접적인 연구가 필요하다. 이에 본 연구에서는 혈관 반응성에 미치는 celecoxib와 aspirin, indomethacin의 영향을 비교 분석하였다. 또한 COX-1, COX-2 단백질 발현에 대한 indomethacin과 NO 공여제의 영향을 조사하였다. Phenylephrine 유발 수축반응에서 전처치 된celecoxib, indometacin, aspirin 순서로 혈관 반응성을 증가시켜, cyclooxygenase를 억제하면 혈관 수축성물질에 대한 반응성이 커질 수 있음을 나타낸다. 이중 cyclooxygenase에 대해 비가역적으로 강한 억제를 나타내는 aspirin이 제일 강한 효과를 나타내어 여기에 대한 연구는 더 필요할 것으로 생각된다. 혈관평활근 세포의 COX-2 단백질 발현은 indomethacin과 SNP, NOR-3 처치에 의해 증가되었으며, LPS를 이용하여 혈관염증을 유발 시키는 경우 혈관평활근 세포의 COX-2 단백질 발현이 증가되었고, 이 상태에서 SNP