L-NAME inhibits Mg(2+)-induced rat aortic relaxation in the absence of endothelium

• Published in: British journal of pharmacology Vol. 128; no. 2; pp. 493 - 499
• Main Authors: Das, R, Kravtsov, G M, Ballard, H J, Kwan, C Y
• Format: Journal Article
• Language: English
• Published: England 01.09.1999
• Subjects: Acetylcholine - pharmacology; Animals; Aorta, Thoracic - drug effects; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Enzyme Inhibitors - pharmacology; In Vitro Techniques; Isometric Contraction - drug effects; Magnesium - antagonists & inhibitors; Magnesium - pharmacology; Male; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; omega-N-Methylarginine - pharmacology; Potassium Chloride - pharmacology; Rats; Rats, Sprague-Dawley
• ISSN: 0007-1188
• DOI: 10.1038/sj.bjp.0702737

1 L-NG-nitro-arginine methyl ester (L-NAME; 100 microM), a nitric oxide synthase (NOS) inhibitor, reversed the relaxation induced by 3 microM acetylcholine (ACh) and 2-10 mM Mg2+ in endothelium-intact (+E) rat aortic rings precontracted with 1 microM phenylephrine (PE). In PE-precontracted endothelium-denuded (-E) rat aorta, 3 microM 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 microM ACh were not significantly different. 3 L-NAME (100 microM) also reversed Mg(2+)-relaxation of -E aorta pre-contracted with 20 mM KCl or 10 microM prostaglandin F2alpha (PGF2alpha). L-NG-monomethyl-arginine (L-NMMA; 100 microM) was also effective in reversing the Mg(2+)-relaxation. 4 Addition of 0.2 mM Ni2+, like Mg2+, caused relaxation of PE-pre-contracted -E aorta, which was subsequently reversed by 100 microM L-NAME. 5 Reversal of the Mg(2+)-relaxation by 100 microM L-NAME in PE-precontracted -E aorta persisted following pre-incubation with 1 microM dexamethasone or 300 microM aminoguanidine (to inhibit the inducible form of NOS, iNOS). 6 Pretreatment of either +E or -E aortic rings with 100 microM L-NAME caused elevation of contractile responses to Ca2+ in the presence of 1 microM 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.