Dear Editor, Cyclic guanosine 3’, 5’ monophosphate (CGMP), as a second messenger, plays a key role in cell proliferation, differentiation, and apoptosis. It is formed by guanylyl cyclase (GC) from its precursor, guanosine triphosphate (GTP) (1). GC enzymes can be found in 2 major forms: soluble or cytosol form (sGC) and particulate or transmembrane form (pGC) (1).

Objectives: Cardiovascular disease is a major cause of morbidity and mortality in the world. Compared to men of similar age, pre-menopausal women have significantly lower incidence of adverse cardiovascular event including coronary heart disease, essential hypertension and stroke. The incidence of these disorders increases in women with absence of functional ovaries. Estrogen therapy of post menopausal women reduces the incidence of these diseases. This beneficial effect of estrogen may have several mechanisms. The vas ore lax ant effect of estrogens on vasculature is one f the important cardio protective effects. The exact underlying molecular mechanism of this estrogen-induced vasodilatation has not yet been determined. Considering the important roles of veins in preload and heart failure and coronary artery diseases, in this study the acute relaxant effect of 17 b-estradiol and role of endothelium and cyclic guanosin mono phosphate (CGMP) on this effect has been investigated on human saphenous vein. Methods: Rings of human saphenous vein with 3-5 mm length were prepared and equilibrated in Krebs solution under 3 g tension (37°C; 95% O2 ; 5% CO2) for 60 min. In the various experiments, the vascular rings were contracted with prostaglandin F2a(PGF2a, 1.5µM) or potassium chloride (KCl, 60 mM). When contraction was stable 17 b-estradiol was applied for 40 minutes in the presence or absence of endothelium and different inhibitors. Relaxation was expressed as % reversal of contraction induced by vasoactive agents. Results: 17 b-estradiol (5-40 µM) elicited a concentration-dependent relaxation of KCI- and PGF2a -induced active tone in human saphenous vein rings. Incubation of veins for 20 min with methylen blue or N-nitro-L-arginine methyl ester (L-NAME) reduced the relaxant effect of estrogen, significantly (p<0.05). This reduction was disappeared by denuding endothelium. However, when intact tissues were incubated with 10 µM indomethacin, cycloxygenase inhibitor or 1µM KT5823, a protein kinase G inhibitor or cyclohexamide (100 µM) or puromycin (10µM) protein synthetase inhibitors, the vasorelaxant effect of 17 b-estradiol on PGF2a -induced contraction was not modified significantly (p>0.05). Conclusion: These results suggest that 17 b-estradiol induces dose dependent vasorelaxant effect in human saphenous vein, at least partially, by nitric oxide production and this relaxant effect is independent of CGMP, cycloxygenase or genomic pathways.

Background and aim: Nitric oxide (NO), an active and non-stable compound, has been shown to regulate many sperm functions such as acrosome reaction and sperm chemotaxis. The aim of this study was to investigate the effects of NO and CGMP in the progressive motility of human sperm. Methods: After incubation of twenty normozoospermic samples for 90 minutes in the presence of ODQ (soluble guanylate cycles inhibitor), GSNO (NO donor), 8-br-CGMP (CGMP analogue) and ODQ+GSNO, the progressive motility were assessed by CASA system. Data were analyzed using paired t test.Results: Progressive motilities of sperm increased 4.1% in intubation with GSNO at min 90th (p<0.05) and 4% in intubation with 80bromo-CGMP at min 60 (p<0.05). ODQ significantly (p<0.05) decreased progressive motility in the amounts of 10.7% at 30 minutes, 11.2% at 60 minutes and 12.2% at 90 minutes compared with their controls. ODQ+GSNO also significantly (p<0.05) caused to be decreased progressive motility in the amounts of 9.7%, 10.8% and 9.9% orderly at 30, 60 and 90 minutes in comparison to their controls (p<0.05).Conclusion: NO regulates the progressive motility of human spermatozoa via CGMP synthesis.

The principal roles of the cyclic nucleotides in regulating sperm functions are well established, but the factors controlling their generation and actions have not yet been entirely understood. In particular, specific roles for cyclic GMP (CGMP) in mammalian sperm are poorly understood. In this study, we have characterized comparatively the cAMP and CGMP signaling systems in ejaculated human sperm. Mean concentrations of CGMP (0.1 µM) were found to be 100-fold lower than those of cAMP in non-stimulated cells, and adenylyl cyclase (AC) activities predominated by far over guanylyl cyclase (GC) activities in both paniculate and soluble protein fractions. By different experimental approaches (photoaffinity labeling, cyclase assays, and immunoblotting), we provided evidence for the presence or absence of different factors involved in either cAMP or CGMP pathways; the factors present consisted of guanylyl cyclase-A, soluble guanylyl cyclase, and regulatory and catalytic subunits of cAMP-dependent protein kinase, while the absent ones included guanylyl cyclase-B, natriuretic peptide clearance receptor, neuronal nitric oxide synthase, and CGMP-dependent protein kinsae I. Functional studies showed that CGMP, at high concentrations, can enhance sperm protein tyrosine phosphorylation, but not serine phosphorylation of glycogen synthase kinase. This study reveals that human sperm are characterized by an exceptional predominance of cAMP signaling and indicates potential roles for CGMP.

Millions of people worldwide have Alzheimer's disease, and with the disproportionate growth of the elderly population, the disease, which is the most common form of dementia among the elderly, is becoming a public health crisis. This study aimed to investigate the effect of endurance training before and after Alzheimer's induction on some neuroplasticity-related factors in the hippocampus of male Wistar rats. Before inducing Alzheimer's disease, 32 8-week-old male rats weighing an average of 250 g were randomly allocated into two groups: rest (16 heads) and exercise (16 heads). Each group was divided into two subgroups after four weeks (the first and second weeks at a speed of 10 meters per minute in two 15-minute shifts, the third week at a speed of 15 meters per minute in three 15-minute shifts, and the fourth week at a speed of 15 meters per minute in four 15-minute shifts with 5-minute intervals). 1. amyloid beta injection and 2. without injection. After 72 hours, the animals were killed and their hippocampus was removed for examination. Real Time PCR measured BDNF, PKG, and CGMP gene expression. Data were analyzed by one-way analysis of variance and Tukey post hoc test at the significant level of p <0. 05. The results showed that the levels of BDNF, PKG and CGMP in the exercise group were significantly higher than the rest group in the stage after Alzheimer's induction (p = 0. 001). According to the results, it seems that aerobic exercise can help improve neuroplasticity in the hippocampus of Alzheimer's mice.

Background: CD24 is a cell adhesion molecule that has been implicated in metastatic tumor progression cells. Our aim was to clarify the correlation between CD24 expression and cAMP: CGMP ratio in murine colorectal cancer cell line (CT26) after using cholera toxin.Materials and Methods: The CT26 cells were cultured in flasks for assaying cAMP and CGMP by ELISA kits, also the cells were cultured in flasks for assaying cytoplasmic and membranous CD24 expression. The Real-Time PCR was done for cDNA that was synthesized from CT26 cells’ mRNA. Also, expression CD24 marker of cells was determined by Anti-CD24 antibody and Goat Anti-Rabbit IgG-FITC (flow cytometry).Results: The cholera toxin increases the cAMP: CGMP ratio and influenced the cytoplasmic and membrane CD24 expression level.Conclusion: Cholera toxin increased cAMP. After increasing cAMP/CGMP ratio, cytoplasmic and membranous CD24 expression showed decline.

Background and purpose: Hypertension is a global health challenge due to its high prevalence and increased risk of cardiovascular disease. It is a multifactorial disease in which both genetic and environmental factors are involved. So far, a number of genes and pathways have been proposed to be associated with HTN, including the nitric oxide/CGMP pathway. To further clarify the role of NO /CGMP in the pathogenesis of HTN and also to find genetic determinants of predisposition to HTN in Kermanshah province, Iran, we aimed to investigate the association between three key points in nitric oxide signaling pathway, namely eNOS, GUCY1A3, and PDE1A genes, and susceptibility to hypertension. Materials and methods: In this case-control study, a total of 130 patients and 110 healthy subjects were enrolled. Three polymorphisms (rs1799983 in eNOS gene, rs13139571 in GUCY1A3 genes and rs16823124 in PDE1A gene) were investigated by PCR-RFLP method. Data were then statistically analyzed. Results: This study showed a significant association between the genotypic and allelic frequencies of the rs1799983 polymorphism in the eNOS gene and the rs13139571 gene in GUCY1A3 (P<0. 05), while there was no significant association with PDE1A (P>0. 05). However, the interaction with the other two SNPs may confer susceptibility to hypertension.