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

Abstract

1 L-N G -nitro-arginine methyl ester (L-NAME; 100 mM), a nitric oxide synthase (NOS) inhibitor, reversed the relaxation induced by 3 mM acetylcholine (ACh) and 2 ± 10 mM Mg 2+ in endotheliumintact (+E) rat aortic rings precontracted with 1 mM phenylephrine (PE). In PE-precontracted endothelium-denuded (7E) rat aorta, 3 mM ACh did not, but Mg 2+ caused relaxation which was reversed by L-NAME, but not by D-NAME. 2 The concentration response pro®les of L-NAME in reversing the equipotent relaxation induced by 5 mM Mg 2+ and 0.2 mM ACh were not signi®cantly di erent. 3 L-NAME (100 mM) also reversed Mg 2+ -relaxation of 7E aorta pre-contracted with 20 mM KCl or 10 mM prostaglandin F 2a (PGF 2a ). L-N G -monomethyl-arginine (L-NMMA; 100 mM) was also e ective in reversing the Mg 2+ -relaxation. 4 Addition of 0.2 mM Ni 2+ , like Mg 2+ , caused relaxation of PE-pre-contracted 7E aorta, which was subsequently reversed by 100 mM L-NAME. 5 Reversal of the Mg 2+ -relaxation by 100 mM L-NAME in PE-precontracted 7E aorta persisted following pre-incubation with 1 mM dexamethasone or 300 mM aminoguanidine (to inhibit the inducible form of NOS, iNOS). 6 Pretreatment of either +E or 7E aortic rings with 100 mM L-NAME caused elevation of contractile responses to Ca 2+ in the presence of 1 mM PE. 7 Our results suggest that L-NAME exerts a direct action on, as yet, unidenti®ed vascular smooth muscle plasma membrane protein(s), thus a ecting its reactivity to divalent cations leading to the reversal of relaxation. Such an e ect of L-NAME is unrelated to the inhibition of endothelial NOS or the inducible NOS.

The nitric oxide synthase inhibitor, Ng‐nitro‐l‐arginine‐methyl‐ester, attenuates the delay in gastric emptying induced by hyperglycaemia in healthy humans

“…The dose of l ‐NAME used was based on previous studies 20,28 and, as previously observed, 20,28 changes in cardiovascular function were consistent with NO synthase inhibition. We cannot, however, exclude the possibility that some of the effects of l ‐NAME that we observed were not related to nitrergic mechanisms 29 . Three‐dimensional ultrasound was chosen to measure gastric emptying because of its superior accuracy over 2D ultrasound, 21 and non‐invasive nature, and because no ionizing radiation is required, unlike scintigraphy 22 .…”

“…We cannot, however, exclude the possibility that some of the effects of L-NAME that we observed were not related to nitrergic mechanisms. 29 Three-dimensional ultrasound was chosen to measure gastric emptying because of its superior accuracy over 2D ultrasound, 21 and noninvasive nature, and because no ionizing radiation is required, unlike scintigraphy. 22 Three-dimensional ultrasound has also been validated against scintigraphy for the measurement of gastric emptying of a liquid meal in healthy subjects.…”

Evidence For The Existence Of A Constitutive Nitric Oxide Synthase In Vascular Smooth Muscle

“…We have recently reported 3 that 100 μmol/L L ‐NAME reversed the relaxation induced by 3 μmol/L acetylcholine (ACh) and 2–10 mmol/L Mg 2+ in endothelium‐intact (+E) rat aortic rings precontracted with 1 μmol/L PE with a similar IC 50 at equipotent concentrations of ACh and Mg 2+ . In PE‐precontracted endothelium‐denuded (–E) rat aorta, ACh did not, but Mg 2+ did, cause relaxation that was reversed by L ‐NAME, but not by D ‐NAME.…”

Exercise Training Enhances Vasodilation Responses to Vascular Endothelial Growth Factor in Porcine Coronary Arterioles Exposed to Chronic Coronary Occlusion

“…Furthermore, 10 mol/L L-NMMA does not affect basal diameter or basal NO release 37 measured in isolated arterioles and is without nonspecific smooth muscle effects observed at higher concentrations. 38 Nonetheless, our findings prompted experiments to further define the mechanisms by which VEGF 165 caused vasodilation in coronary arterioles from our model. VEGF stimulates production of NO and prostacyclin, which increase vessel permeability, induce endothelial cell proliferation and migration, 30,39,40 and cause vasodilation 25 and hypotension.…”