혈관평활근세포에서 Cyclosporin A에 의한 Nitric Oxide 생성억제를 길항하는 실험적 중재법

• 영문명: Experimental Intervention to Reverse Inhibition of Nitric Oxide Production by Cyclosporin A in Rat Aortic Smooth Muscle Cells
• 발행기관: 대한약리학회
• 저자명: 김인겸(In Kyeom Kim)
• 간행물 정보: 『대한약리학잡지』제32권 제2호, 211~220쪽, 전체 10쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1996.09.30

영문 초록

The inhibitory effect of cyclosporin A (CsA) on nitric oxide production is not related to the immunosuppressive action of the drug, but to the renal toxicity and arterial hyper-tension. In this study the experimental interventions to reverse the inhibition of nitric oxide production by cyclosporin A in rat aortic smooth muscle cells were examined. CsA inhibited the accumulation of nitrite, the stable end product of nitric oxide, in culture media in a concentration (0.1 ~ 100μg/ml)-dependent manner. The inhibitory effect of CsA on nitrite accumulation were not antagonized by arginine (10 mM), a substrate of nitric oxide synthase, nor by calcium ionophore A23187 (7μM). Forskolin, an activator of adenylate cyclase, which enhanced iNOS induction at transcriptional level, completely reversed the inhibitory action of CsA on nitrite accumulation. However, PMA (2 nM) and PDB (50 nM), PKC activators, increased the inhibitory action of CsA on nitrite accumulalion. From these results, it is suggested that cyclic AMP-elevating agents may be candidates of therapeutic agents in prevention and treatment of renal toxicity and arterial hypertension induced by CsA. Among conventional antihypertensive drugs, calcium channel blockers and α-blockers are preferred to β-blockers.

키워드

Cyclosporin A Nitric oxide synthase Nitrite VSMC Forskolin