Nitric oxide synthesis inhibition suppresses implantation and decreases cGMP concentration and protein peroxidation.

The effect of Nw-nitro-L-arginine on embryonic implantation and cGMP carbonyl group concentration was assessed at the rat implantation site (IS) and non-implantation site (NIS). The intraluminal administration of 25 microg (2.3 mM) of Nw-nitro-L-arginine inhibited implantation in 34.7% and embryo survival (100%), while in addition, decreasing cGMP concentration both at the site (1664.2 +/- 333.8 pmoles/mg of protein for the control and 1321 +/- 384.3 for those treated), as well as at the NIS (1203.7 +/- 200 to 780.2 +/- 168.5). Carbonyl group concentration was considerably less at the implantation site treated with Nw-nitro-L-arginine than in the control (0.062 +/- 0.012 nmoles/mg of protein and 0.45 +/- 0.1, respectively). Nonetheless, the NIS was not significantly different (0.12 +/- 0.04 and 0.15 +/- 0.05). Our results show that a nitric oxide (NO) dependent system parallel to the formation of cGMP and protein peroxidation products is important at the blastocyst implantation site in order for the endometrium to acquire the necessary properties for an adequate receptivity.

[Nitric oxide as a regulator of hemodynamic changes in pregnancy]. / El óxido nítrico como regulador de los cambios hemodinámicos en la gestación.

Nitric oxide (.NO) produced by the majority of animal cells, has been considered a second messenger, since it is the result of a transduction process induced by a first stimulus. Biochemically, .NO is produced during the conversion of L-arginine to L-citruline by a reaction catalyzed by the enzyme nitric oxide synthetase. Two ixoenzymes have been characterized from this enzyme: a constitutive isoenzyme activated by hormones produced by the endothelial cells and acting on smooth muscle relaxing properties and the other, an inducible isoenzyme whose synthesis is stimulated by cytokines, and produced by macrophages. As pregnancy progresses, the concentrations of .NO, its metabolites, nitrates and nitrites, cGMP and the synthesizing enzyme, nitric oxide synthetase, increase parallelly until reaching a maximum peak before birth. It is considered that .NO is the molecule that maintains the typical vasodilated tone during pregnancy. During preeclampsia, this free radical, as well as its metabolites are found to be significantly decreased, in addition, the administration of .NO donors or of the precursor of L-arginine reverts the vascular abnormalities of this condition. The mechanism of action behind .NO on the vascular endothelium is by its stimulating effect on the enzyme cyclase guanilate, causing an increase in cGMP concentration and the relaxation of the smooth muscle. The nitric oxide generates by macrophages acts as a defense mechanism when linked with other radicals as the superoxide anion (O2).

[Importance of free radicals during the reproduction cycle]. / Importancia de los radicales libres durante el ciclo reproductor.

The peroxidation products, the free radicals, and the antioxidants compounds notable increase during ovulation, implantation, and pregnancy evolution. Superoxide anion (O2-) rise six time more on the proestrous, than on other stages, while its regulation enzyme, the superoxide dismutase (SOD), decreases. The presence of superoxide anion is related with the edema and the cellular proliferation on the estrous. Superoxide anion is also connected with the increase of fluidity and polarity of the membranes during the implantation. As the pregnancy elapse the lipoperoxides products and the antioxidant compounds augment suggesting that lipoperoxides evoke defense mechanism in a way that, at the end of the pregnancy, the antioxidants exceed peroxidative phenomena. By the other hand, the nitric oxide radical has gained great importance during the pregnancy because it is considered one of the most powerful relaxants of smooth muscle. The inhibition of its synthesis provokes similar signs to the preeclampsia and tis administration can revert many vascular alterations. The role of free radicals is not limited to dangerous effects, but it also, in adequate concentrations, includes the as stimulators of grown factors, and participants of the membranes fluidity.