IJCS | Volume 32, Nº2, May/June 2019

213 Figure 5 - Concentration-response curve for CLAE (1, 3, 10, 30, 100, 300 and 1000 µg/mL) in rat isolated thoracic aorta annulus without endothelium pre-contracted with PHE, KCl 20 and KCl 80. The dots represent the mean ± SD of the concentrations used with n = 6 and # (p < 0.01) versus KCl 20. % RELAXATION AECL Brozzo et al. Curcuma longa abolishes contractions in the aortic artery Int J Cardiovasc Sci. 2019;32(3)207-216 Original Article AECL effect on the contraction caused by blocking the intracellular K + efflux In annuli without endothelium, although with much less significance, the AECL continued to show a significant vasorelaxant activity (p < 0.01). The AECL- induced response in the isolated thoracic aortic annuli of rats precontracted with 20 mM KCl was significantly (p < 0.01) lower than the AECL-induced vasorelaxation on PHE-induced contraction in (E-) annuli (Figure 5). The percentage of vasorelaxation over the 20 mM KCl contraction was 56.98% and 31.56%, over the 80 mMKCl contraction. Therefore, it seems that the effect of AECL has a greater significance for the opening of K + channels than for the blockade of voltage-operated calcium channels (VOCCs) (Figure 5). Discussion In the first approach (Figure 1) with (E + ) and (E-) annuli, it was observed that the AECL effect strongly depends on factors derived from the vascular endothelium, due to its greater relaxation in E + annuli. The vascular endothelium, through the layer of cells that covers it internally, produces different mediating substances that regulates the vascular smooth muscle tone. 18-23 There is a natural control of these mediators’ release, and at the limit of the physiological functions, the release of the relaxant factors precedes the contracting agents, 19 of which NO is the first to be released, followed by prostacyclin and other endothelium-derived relaxant agents. 20 In many studies, the NO produced by endothelial cells with physiological vasodilation function 21,22 has been indicated as the main relaxant factor derived from the vascular endothelium. It crosses space from the endothelium to the vascular smooth muscle, promoting the relaxation of this musculature cells, 23 acting by stimulating the guanylyl cyclase of the cytoplasm soluble fraction, converting Guanosine triphosphate (GTP) into cyclic Guanosine Monophosphate (cGMP), which is the second messenger responsible for the vascular relaxant effect. 24 In the NO synthesis, first the hydroxylation of one of the guanidine nitrogens of L-arginine occurs to generate NG-hydroxy-L-arginine (NHA), followed by the conversion of NHA into NO and citrulline. 25 All NOS (Nitric Oxide synthase) isoforms can be inhibited by L-arginine analogs, such as NG-monomethyl-L- arginine (L-NMMA), N-imino-ethyl-L-ornithine (L-NIO), NG-amino-L-arginine (L-NAA), NG-nitro-L-arginine