신성 고혈압 쥐에서 SNAP에 의한 혈관 이완작용에 있어 Ca2＋ 의존성 K＋-통로의 역할 = Role of KCa Channels in SNAP-Induced Relaxation of Aorta from Renal Hypertensive Rats

국문 초록 (Abstract)

목 적 : S-nitroso-N-acetylpenicillamine (SNAP)에 의한 혈관 이완반응에 있어 cGMP 및 Ca2＋ 의존성 K＋ (KCa)-통로의 활성을 검토하고 two-kidney, one clip (2K1C) 신성고혈압 모델에서 차이가 있는지 구명하고자 본 연구를 시행하였다.방 법 : 흰쥐 일측 신동맥에 clip을 장치한 고혈압군과 대조군의 적출 흉부 대동맥 표본을 methylene blue (MB) 및 iberiotoxin (ITX)으로 전처치한 상태에서 phenylephrine (PE)으로 수축시킨 후 SNAP으로 이완시켜 그 반응을 양군에서 비교 검토하였다.결 과 : PE에 의한 수축반응은 2K1C 고혈압군에서 대조군에 비해 항진되었다. PE의 수축반응은 MB 전처치시 대조군에서 증가되었으나 고혈압군은 영향받지 않았으며 ITX에 의해서는 양군 모두 변화가 없었다. SNAP에 의한 이완반응은 고혈압군과 대조군에서 유사한 양상을 보였다. MB는 SNAP의 이완반응을 억제시켰으며 그 정도는 고혈압군과 대조군에서 차이가 없었다. ITX는 SNAP의 이완반응을 대조군에서 억제시켰으나 고혈압군에는 영향을 미치지 않았다.

다국어 초록 (Multilingual Abstract)

Purpose : S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, is thought to relax vascular smooth muscle by stimulation of soluble guanylate cyclase, accumulation of its product cyclic GMP (cGMP) level. Evidence has emerged that NO-induced vasodilatation is also mediated by stimulating Ca2＋-activated K＋ (KCa) channels directly or indirectly through cGMP. The aim of the present study was to investigate possible involvement or alteration of KCa channels in the mechanism of vasodilation induced by SNAP in two-kidney, one-clip (2K1C) hypertensive rats.
Methods: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Using rings prepared from thoracic aortae, we studied changes in isometric tension of the rings in response to SNAP to evaluate effects of a soluble guanylate cyclase inhibitor methylene blue (MB), and a specific blocker of KCa channel iberiotoxin (ITX).
Results : Aortic rings from 2K1C hypertensive and sham-clipped control rats precontracted with phenylephrine showed similar relaxation to SNAP. MB markedly suppressed the SNAP-induced relaxation in both groups, leaving about 30% of MB-resistant relaxation. ITX nearly completely eliminated the MB-resistant relaxation in control rats, but it did not affect 2K1C rats.
Conclusion: These results suggest that SNAP-induced vasorelaxation is mediated through cGMP- dependent and cGMP-independent KCa channel involving mechanisms, the latter may be altered in 2K1C renal hypertension.

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