신성 고혈압쥐에서 SNAP에 의한 혈관 이완작용에 있어 Ca2+ 의존성 K-통로의 역할

Abstract

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 the possible involvement or the alteration of KCa channels in the mechanism of vasodilation induced by SNAP in two-kidney, one clip(2K1C) hypertensive rats. 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). 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 in 2K1C rats. These results suggest that SNAP-induced vasorelaxation is mediated through cGMP-dependent and cGMP-independent KCa channel involvings mechanisms, the latter may be altered in 2K1C renal hypertension. Key words: NO donor, KCa channel, Vasorelaxation, Renal hypertension.