Vasorelaxant effects of pramanicin, an anti-fungal agent: selective action on endothelial cells

Japanese Journal of Pharmacology
C Y KwanE E Daniel

Abstract

A newly discovered antifungal agent, pramanicin, within the therapeutically effective concentration range (4-100 microM), inhibits the tone of phenylephrine (PE)-precontracted dog carotid arterial rings in a concentration-dependent manner and leads to gradual development of relaxation. However, pramanicin had no effect on rings precontracted with 100 mM KCl or on endothelium-denuded rings. Thus, inhibition by pramanicin of PE-induced contraction was endothelium-dependent. Preincubation of 100 microM pramanicin with carotid arterial rings for 30 min did not significantly affect the concentration-contraction response to PE, but almost completely inhibited the endothelium-dependent relaxation response to subsequent addition of 3 microM carbachol or 100 microM pramanicin. This irreversible inhibition of endothelium-dependent relaxation, which is independent of extracellular Ca2+, suggests possible endothelial cell damage by pramanicin. Pretreatment of the endothelium-intact vascular rings with L-N(G)-nitro-arginine (100 microM) inhibited the relaxation of PE-precontracted rings induced by 3 microM carbachol or 100 microM pramanicin, suggesting that the generation of nitric oxide (NO) in endothelial cells mediates the slow vascular ...Continue Reading

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Citations

May 24, 2008·Journal of Lipid Research·Sarah T PruettAlfred H Merrill
Jun 8, 2002·Life Sciences·Ruth K WilsonGeorge J Sorger
Aug 2, 2003·Journal of Pharmacological Sciences·Chiu-Yin KwanDavid Liscombe
May 4, 2011·Organic & Biomolecular Chemistry·Seokwoo LeeSanghee Kim
Dec 12, 2012·Chembiochem : a European Journal of Chemical Biology·Daniela Boettger, Christian Hertweck

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