Biomedical Research

The present study was aimed to examine the effects of three quaternary ammonium ions on both endothelial and exogenous nitric oxide (NO)-mediated relaxation in the rat aorta and to examine whether L-arginine could antagonize the inhibitory effects on endothelial NO-dependent vascular responses. In endothelium-intact aortic rings, cyclopiazonic acid (CPA) induced relaxation with a pD2 of 6.40 ± 0.06. This relaxation was attenuated after treatment with tetrabutyalmmonium (TBA+), tetrapentylammonium (TPA+), or tetraoctylammonium (TOA+) ions, each at 3 μM or with NG-nitro-L-arginine methyl ester (L-NAME) at 100 μM. L-arginine at 1 mM antagonized the inhibitory effect of TBA+ and L-NAME, but not of TPA+ and TOA+. TPA+ and TOA+, but not TBA+, also inhibited endothelium-independent relaxa-tion induced by a NO donor, hydroxylamine. The inhibitory effect of TPA+ was absent in 50 mM K+-containing Krebs solution. These results indicate that (1) TBA+ inhibits endothelial NO-mediated relaxation probably through inhibition of NO production and/or release; (2) TPA+-induced inhibition of endothelial and exogenous NO-dependent relaxation may be me-diated through blockade of K+ channels in aortic smooth muscle; and (3) TOA+ may act on both endothelium and smooth muscle to inhibit NO-mediated vasorelaxant effect.

Author(s): Y Huang, CW Lau, FL Chan, XQ Yao
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