NITROGLYCERIN-INDUCED AORTIC RELAXATION MEDIATED BY CALCIUM-ACTIVATEDPOTASSIUM CHANNEL IS MARKEDLY DIMINISHED IN HYPERTENSIVE RATS

Nitroglycerin (NTG), a nitric oxide (NO) donor, is considered to relax vascular smooth muscle by stimulating soluble guanylate cyclase, whic h in turn increases cyclic GMP (cGMP) level. Recently it became eviden t that NO-induced vasodilatation is also mediated by stimulating Ca-ac tivated K (K-Ca) channels directly and/or indirectly through cGMP. We, therefore, tried to investigate the possible involvement or the alter ation of K-Ca channels in the mechanism of vasodilation induced by NTG in physiological and pathological conditions. Using rings prepared fr om thoracic aortas of spontaneously hypertensive rats (SHR) and those of age-matched Wistar-Kyoto rats (WKY), we studied changes in isometri c tension of the rings in response to NTG to evaluate effects of a sol uble guanylate cyclase inhibitor methylene blue (MB), and a specific b locker of K-Ca channel charybdotoxin (CTX). Rings from WKY and SHR pre contracted with norepinephrine showed similar aortic relaxation to NTG . MB markedly suppressed the NTG-induced relaxation in both strains, l eaving about 30% of MB-resistant relaxation. CTX nearly completely eli minated this MB-resistant relaxation in WHY but did not affect this re laxation in SHR. These results suggest that NTG-induced vasorelaxation is mediated through i) cGMP-dependent and ii) cGMP-independent K-Ca c hannel involving mechanisms, the latter may be diminished or virtually eliminated in hypertensive state.