In vitro effects of nitric oxide synthase inhibition by L-NAME on human internal mammary arteries rings

Authors: Germaine SAVOIU¹, Constantin CRĂCIUN², Carmen CRISTESCU³, Corina ȘERBAN¹*, Daniela IONESCU⁴, Ovidiu FIRA-MLADINESCU¹, Lavinia NOVEANU⁵, Danina MUNTEAN¹, Georgeta MIHALAȘ⁵

Affiliation: ¹ Department of Pathophysiology, University of Medicine and Pharmacy “Victor Babes” Timisoara, Romania; ² Electron Microscopy Center, “Babes-Bolyai“ University, Cluj-Napoca, Romania; ³ Department of Clinical Pharmacy, University of Medicine and Pharmacy “Victor Babes” Timisoara, Romania; ⁴ Department of Toxicology, University of Medicine and Pharmacy “Victor Babes” Timisoara, Romania; ⁵ Department of Physiology, University of Medicine and Pharmacy “Victor Babes” Timisoara

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ABSTRACT. Human internal mammary arteries (IMA) are relatively protected from atherosclerosis. The aim of the present study was to investigate the effect and mechanism of action of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on human mammary artery (IMA) segments. Segments of IMA were obtained from 12 patients who underwent coronary artery bypass graft surgery. They were cut into rings, suspended between two wire hooks in organ bath chambers and constricted submaximally with Phenylephrine. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. The dose-effect graphs were determined for the following substances: 5¢ADP ± L-NAME in concentrations between 10^-9 and 10^-4M on the precontracted rings by 10^-5M Phenylephrine and NSP ± L-NAME for concentrations between 10^-9 and 10^-4M, on the precontracted rings by 10^-5M Phenylephrine. The administration of the pharmacological agents was performed in a cumulative manner, the concentration being expressed in absolute values (cN), and the relaxation as % of the tension induced by the pre-contraction with 10^-5M Phenylephrine. In our study, the incubation of the human artery mammary rings for 30 minutes with 10^-5M L-NAME determined a significant increase of contractile response to 10^-5M Phenylephrine (p < 0.001), a significant decrease of response to 5’ADP (p < 0.001) and absence of modification of the endothelial-independent response to NSP (p = 0.03). The results of our study showed that, in the case of a rigorous standardized methodology, the experimental protocol study of a vasomotor function of endothelium, in our case human arterial mammary artery, it can reveal endothelial dysfunction. The exposure to an inhibitor of NO Synthase Inhibitor L-NAME, (N (G)-nitro-L-arginine methyl ester), has to attenuate significant the vasodilator response of the vascular ring to Phenylephrine.

Keywords: endothelium, nitric oxide, L-NAME