L‐NAME inhibits Mg2+‐induced rat aortic relaxation in the absence of endothelium
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abstract
L‐NG‐nitro‐arginine methyl ester (L‐NAME; 100 μM), a nitric oxide synthase (NOS) inhibitor, reversed the relaxation induced by 3 μM acetylcholine (ACh) and 2–10 mM Mg2+ in endothelium‐intact (+E) rat aortic rings precontracted with 1 μM phenylephrine (PE). In PE‐precontracted endothelium‐denuded (−E) rat aorta, 3 μM ACh did not, but Mg2+ caused relaxation which was reversed by L‐NAME, but not by D‐NAME.The concentration response profiles of L‐NAME in reversing the equipotent relaxation induced by 5 mM Mg2+ and 0.2 μM ACh were not significantly different.L‐NAME (100 μM) also reversed Mg2+‐relaxation of −E aorta pre‐contracted with 20 mM KCl or 10 μM prostaglandin F2α (PGF2α). L‐NG‐monomethyl‐arginine (L‐NMMA; 100 μM) was also effective in reversing the Mg2+‐relaxation.Addition of 0.2 mM Ni2+, like Mg2+, caused relaxation of PE‐pre‐contracted −E aorta, which was subsequently reversed by 100 μML‐NAME.Reversal of the Mg2+‐relaxation by 100 μML‐NAME in PE‐precontracted −E aorta persisted following pre‐incubation with 1 μM dexamethasone or 300 μM aminoguanidine (to inhibit the inducible form of NOS, iNOS).Pretreatment of either +E or −E aortic rings with 100 μML‐NAME caused elevation of contractile responses to Ca2+ in the presence of 1 μM PE.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.British Journal of Pharmacology (1999) 128, 493–499; doi:10.1038/sj.bjp.0702737
