L-NAME inhibits Mg2+-induced rat aortic relaxation in the absence of endothelium

被引:16
作者
Das, R
Kravtsov, GM
Ballard, HJ
Kwan, CY
机构
[1] McMaster Univ, Fac Hlth Sci, Dept Med, Hamilton, ON L8N 3Z5, Canada
[2] Univ Hong Kong, Fac Med, Dept Physiol, Hong Kong, Peoples R China
关键词
L-NAME; magnesium; calcium; endothelium; nitric oxide; vascular smooth muscle; aorta;
D O I
10.1038/sj.bjp.0702737
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 L-N-G-nitro-arginine methyl ester (L-NAME; 100 mu M), a nitric oxide synthase (NOS) inhibitor, reversed the relaxation induced by 3 mu M acetylcholine (ACh) and 2-10 mM Mg2+ in endothelium-intact (+E) rat aortic rings precontracted with 1 mu M phenylephrine (PE). In PE-precontracted endothelium-denuded (-E) rat aorta, 3 mu M ACh did not, but Mg2+ caused relaxation which was reversed by L-NAME, but not by D-NAME. 2 The concentration response profiles of L-NAME in reversing the equipotent relaxation induced by 5 mM Mg2+ and 0.2 mu M ACh were not significantly different. 3 L-NAME (100 mu M) also reversed Mg2+-relaxation of -E aorta pre-contracted with 20 mM KCI or 10 mu M prostaglandin F-2 alpha (PGF2 alpha). L-N-G-monomethyl-arginine (L-NMMA; 100 mu M) was also effective in reversing the Mg2+-relaxation. 4 Addition of 0.2 mM Ni2+, like Mg2+, caused relaxation of PE-pre-contracted -E aorta, which was subsequently reversed by 100 mu M L-NAME. 5 Reversal of the Mg2+-relaxation by 100 mu M L-NAME in PE-precontracted -E aorta persisted following pre-incubation with 1 mu M dexamethasone or 300 mu M aminoguanidine (to inhibit the inducible form of NOS, iNOS). 6 Pretreatment of either +E or -E aortic rings with 100 mu M L-NAME caused elevation of contractile responses to Ca2+ in the presence of 1 mu M PE. 7 Our results suggest that L-NAME exerts a direct action on, as yet, unidentified vascular smooth muscle plasma membrane protein(s), thus affecting its reactivity to divalent cations leading to the reversal of relaxation. Such an effect of L-NAME is unrelated to the inhibition of endothelial NOS or the inducible NOS.
引用
收藏
页码:493 / 499
页数:7
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