Anti-cancer effects of selective cannabinoid agonists in pancreatic and breast cancer cells.

OBJECTIVE: Cancer ranks first among the causes of morbidity and mortality all over the world, and it is expected to continue to be the main cause of death in the coming years. Therefore, new molecular targets and therapeutic strategies are urgently needed. In many cases, some reports show increased levels of endocannabinoids and their receptors in cancer, a condition often associated with tumour aggressiveness. Recent studies have suggested that cannabinoid-1/2 receptors contribute to tumour growth in a variety of cancers, including pancreatic, colon, prostate, and breast cancer. Understanding how cannabinoids can regulate key cellular processes involved in tumorigenesis, such as: cell proliferation and cell death, is crucial to improving existing and new therapeutic approaches for the cancer patients. The present study was aimed to characterize the in-vitro effect of L-759633 (a selective CB2 receptor agonist), ACPA (a selective CB1 receptor agonist) and ACEA (a selective CB1 receptor agonist) on the cell proliferation, clonogenicity, and apoptosis in pancreatic (PANC1) and breast (MDA-MB-231) cancer cells. METHODS: The viability and/or proliferation of cells were detected by MTS assay. A clonogenic survival assay was used to detect the ability of a single cell to grow into a colony. Apoptosis was determined with Annexin V staining (Annexin V-FITC/PI test) and by analyzing the expression of Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2). RESULTS: We found that selective CB1/2 agonists suppressed cell proliferation, clonogenicity and induced proapoptotic function in human PANC1 pancreatic and MDA-MB-231 breast cancer cells. Based on our findings, these agonists led to the inhibition of both cell viability and clonogenic growth in a dose dependent manner. CB1/2 agonists were observed to induce intrinsic apoptotic pathway by upregulating Bax, while downregulating Bcl-2 expression levels. CONCLUSION: Our data suggests that CB1/2 agonists have the therapeutic potential through the inhibition of survival of human PANC1 pancreatic and MDA-MB-231 breast cancer cells and also might be linked with further cellular mechanisms for the prevention (Fig. 5, Ref. 49).

Zingerone ameliorates oxidative stress and inflammation in bleomycin-induced pulmonary fibrosis: modulation of the expression of TGF-ß1 and iNOS.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with limited treatment options. Zingerone found in ginger (Zingiber officinale L.) has many pharmacological effects, especially antiinflammatory and antioxidant activity. However, the effect of zingerone on pulmonary fibrosis (PF) is not fully known. The aim of this study was to investigate the effect of zingerone on bleomycin (BLM)-induced PF and its underlying mechanisms. Wistar-albino rats were given single dose of BLM (5 mg/kg, intratracheal) or vehicle (saline). In treatment groups, zingerone (50 and 100 mg/kg, p.o.) was administered orally for 14 days after BLM administration. Rats and lung tissue were weighed to determine lung index. Antioxidant, antiinflammatory effects, and hydroxyproline content of zingerone were determined by ELISA method. Pulmonary inflammation, collagen deposition, and fibrosis score were determined with Hematoxylin-Eosin (HxE) and Masson's trichrome staining. Transforming growth factor-beta 1 (TGF-ß1) and inducible nitric oxide synthase (iNOS) expressions were detected immunohistochemically. BLM administration increased lipid peroxidation (MDA) and decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. In addition, BLM caused increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-1ß (IL-1ß) in bronchoalveolar lavage fluid (BALF) and accumulation of collagen bundles. Zingerone administration decreased collagen accumulation, TNF-α and IL-1ß levels, MDA level, TGF-ß1, and iNOS expression and increased SOD and GPx activity. Histopathological findings supported the results. These results show that zingerone (50 and 100 mg/kg) at both doses significantly contributes to healing of PF by improving inflammation, oxidative stress, and histopathological alterations and by affecting TGF-ß1 and iNOS signaling pathways.

The effects of mometasone furoate and strontium chloride in a rat model of allergic rhinitis.

Neurogenic inflammation plays a role in the pathophysiology of allergic rhinitis. Highly effective in reducing the sensory irritation caused by some substances, strontium salts directly affect C-type nerve fibers. The aim of this study was to compare the efficacy of mometasone furoate and strontium chloride on early-phase symptoms in a rat model of allergic rhinitis. Wistar albino rats (n = 24) were randomly divided into three groups: the mometasone group, receiving 1 µg mometasone furoate (2 µl/site); the strontium 3% group, receiving 3% strontium chloride (2 µl/site); and the strontium 5% group, receiving 5% strontium chloride (2 µl/site). To induce significant nasal symptoms of allergic rhinitis, 5 µmol of histamine dihydrochloride (HDC) (2 µl/site) was administered. Symptoms of allergic rhinitis were recorded as frequencies of sneezing and nasal rubbing during a 15-minute interval. On days 1 and 2, respectively, 0.9% sodium chloride (NaCl) (2 µl/site to each nasal cavity) and HDC were administered in all of the study groups. On days 3 and 4, the study drugs were administered 10 and 30 minutes before the administration of HDC. On day 5, the study drugs were administered 10 minutes after the administration of HDC. The results of the present study revealed that when strontium chloride or mometasone furoate was administered 30 minutes before the onset of symptoms, a significant decrease was observed in sneezing and nasal rubbing. The number of sneezing occurrences was significantly lower and the number of nasal rubbing occurrences was higher in the strontium 3% group compared to the groups in which mometasone furoate and 5% strontium chloride were administered after onset of symptoms. Recent studies have investigated the efficacy and safety of strontium chloride nasal drops compared with common pharmacologic treatments of allergic rhinitis. These studies have revealed that allergic rhinitis can be successfully and safely treated with strontium-chloride-containing products, thus offering a potential new treatment strategy.

Histopathological evaluation of the effect of locally administered strontium on healing time in mandibular fractures: An experimental study.

BACKGROUND: Mandibular fractures are the most common facial fractures. They can be treated by conservative techniques or by surgery. The authors hypothesized that the application of a single local dose of strontium chloride would accelerate the healing of subcondylar mandibular fractures, shorten the recovery time and prevent complications. OBJECTIVES: The aim of the present pilot study was to evaluate the effects of a single local dose of strontium chloride on the healing of subcondylar mandibular fractures in rats. MATERIAL AND METHODS: This randomized experimental study was carried out on 24 male Wistar albino rats. The rats were randomly divided into 3 groups: experimental group 1, receiving 3% strontium chloride; experimental group 2, receiving 5% strontium chloride; and the control group. A full thickness surgical osteotomy was created in the subcondylar area. A single dose of strontium solution (0.3 cc/site) was administered locally by injection on the bone surfaces of the fracture line created. Nothing was administered to the control group. The mandibles were dissected on postoperative day 21. The fractured hemimandibles were submitted to histopathological examination. RESULTS: The median bone fracture healing score was 9 (range: 7-9) in experimental group 1; 8 (range: 7-10) in experimental group 2; and 7.50 (range: 7-8) in the control group. When the groups were compared in terms of bone healing scores, there was a statistically significant difference between experimental group 1 and the control group (p < 0.05). CONCLUSIONS: This study is the first to show that local strontium may have positive effects on the healing of subcondylar mandibular fractures. In the authors' opinion, 3% strontium was beneficial for accelerating facial skeleton consolidation and bone regeneration in rat subcondylar mandibular fractures. This treatment procedure may be combined with closed fracture treatment or a conservative approach.

Strontium chloride hexahydrate as a candidate molecule for long-term treatment of allergic rhinitis.

BACKGROUND & OBJECTIVES: Neurogenic inflammation plays a role in the pathophysiology of allergic rhinitis (AR). Strontium salts are highly effective in reducing the sensory irritation. This study was aimed to investigate the efficacy of strontium chloride (SC) on AR symptoms based on the duration of SC use before the symptoms begin. METHODS: Wistar albino rats (n=18) were randomly divided into three groups: Group 1, received 1µg mometasone furoate (MF); Group 2, three per cent SC; and Group 3 received five per cent SC (2 µl/site). Drugs were administered to the each nasal cavity for three weeks every morning. On the days 7, 14 and 21, histamine dihydrochloride (HD) 5 µmol (2 µl/site) was administered and the frequencies of nasal rubbing and sneezing were counted for 15 min. RESULTS: After 7, 14 and 21 day medication period, the groups were compared in terms of the frequency of sneezing and nasal rubbing following HD. There was a significant difference among the groups in terms of the frequency of sneezing on the day 7 (PPInterpretation & conclusions: Our results showed that three and five per cent SC were less effective than MF for sneezing during the first week, but the efficiency was equal to that of MF after the first 14 days. Long-term use of SC was as effective as MF on nasal rubbing. SC can be as effective as MF on both sneezing and nasal rubbing on regular use over three weeks.

Effects of a Multikinase Inhibitor Motesanib (AMG 706) Alone and Combined with the Selective DuP-697 COX-2 Inhibitor on Colorectal Cancer Cells.

In the present study, we investigated the effects of motesanib (AMG 706), a multikinase inhibitor alone and in combination with DuP-697, an irreversible selective inhibitor of COX-2, on cell proliferation, angiogenesis, and apoptosis induction in a human colorectal cancer cell line (HT29). Real time cell analysis (RTCA, Xcelligence system) was used to determine the effects on colorectal cancer cell proliferation. Apoptosis was assessed with annexin V staining and angiogenesis was determined with chorioallantoic membrane model. We found that motesanib alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. Combination with DUP-697 increased the antiproliferative, antiangiogenic and apoptotic effects. Results of this study indicate that motesanib may be a good choice in treatment of colorectal tumors. In addition, the increased effects of combination of motesanib with DuP-697 raise the possibility of using lower doses of these drugs and therefore avoid/minimize the dose-dependent side effects generally observed.

Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of D-galactose-induced aging mice.

CONTEXT: Morus nigra L. (Moraceae) has various uses in traditional medicine. However, the effect of M. nigra on cognitive impairment has not been investigated yet. OBJECTIVE: The objective of this study is to determine the phenolic acid content and DNA damage protection potential of M. nigra leaf extract and to investigate the extract effect on cognitive impairment and oxidative stress in aging mice. MATERIALS AND METHODS: Phenolic acid content was determined by quantitative chromatographic analysis. DNA damage protection potential was evaluated on pBR322 plasmid DNA. Thirty-two Balb-C mice were randomly divided into four groups (control, d-galactose, d-galactose + M. nigra 50, and d-galactose + M. nigra 100). Mice were administered d-galactose (100 mg/kg, subcutaneous) and M. nigra (50 or 100 mg/kg, orally) daily for 8 weeks. Behavioral responses were evaluated with Morris water maze. Activities of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed in serum, brain, and liver. RESULTS: In extract, vanillic (632.093 µg/g) and chlorogenic acids (555.0 µg/g) were determined. The extract between 0.02 and 0.05 mg/mL effectively protected all DNA bands against the hazardous effect of UV and H2O2. Morus nigra significantly improved learning dysfunctions (p < 0.01), increased memory retention (p < 0.01), reduced MDA levels (p < 0.05), and elevated SOD, GPx, and CAT activities (p < 0.05) compared with the d-galactose group. DISCUSSION AND CONCLUSION: These results show that M. nigra has the potential in improving cognitive deficits in mice and that M. nigra may be useful to suppress aging, partially due to its scavenging activity of free radicals and high antioxidant capacity.

Perspectives on reasons of medication nonadherence in psychiatric patients.

PURPOSE: This study was carried out to evaluate factors resulting in medication nonadherence within 6 months before admission to the psychiatric service of our hospital for bipolar disorder, schizophrenia/schizoaffective disorder, depression, and other psychiatric diseases. PATIENTS AND METHODS: Two hundred and three patients admitted to the Psychiatry Service of the Medical Faculty were included in this study. Sociodemographic parameters and clinical findings within 6 months before admission and patients' views on reasons of medication nonadherence were examined. RESULTS: Patients were classified into four groups according to their diagnosis: bipolar disorder (n=68, 33.5%), schizophrenia/schizoaffective disorder (n=59, 29.1%), depression (n=39, 19.2%), and others (n=37, 18.2%). The ratio of medication nonadherence was higher in the bipolar disorder group when compared to the groups with schizophrenia/schizoaffective disorder, depression, and other disorders (12.1%, 18.2%, and 24.2% vs 45.5%); however, the ratio of medication nonadherence was similar in schizophrenia/schizoaffective disorder, depression, and the others group. In logistic regression analysis, irregular follow-up (odds ratio [OR]: 5.7; 95% confidence interval [CI]: 2.92-11.31) and diagnosis (OR: 1.5; 95% CI: 1.07-1.95) were determined to be important risk factors for medication nonadherence. The leading factors for medication nonadherence were: "not willing to use medication", "not accepting the disease", and "being disturbed by side effects" in the bipolar disorder group, "not accepting the disease" in the schizophrenia/schizoaffective disorder group, "feeling well" in the depression group, and "being disturbed by side effects" in the other diseases group. CONCLUSION: Medication nonadherence is an important problem in psychiatric patients and should be dealt with by taking into account the diagnosis, attendance to follow-up appointments, and the patient's attitude. Ensuring regular attendance to follow-up appointments, adjusting the management plan according to the diagnosis, and improving their thoughts about resistance to medication can be beneficial in terms of medication adherence.

Effect of Capparis spinosa L. on cognitive impairment induced by D-galactose in mice via inhibition of oxidative stress.

BACKGROUND/AIM: To determine the phenolic acid levels and DNA damage protection potential of Capparis spinosa L. seed extract and to investigate the effect of the extract on cognitive impairment and oxidative stress in an Alzheimer disease mice model. MATERIALS AND METHODS: Thirty BALB/c mice divided into 5 groups (control, D-galactose, D-galactose + C. spinosa 50, D-galactose + C. spinosa 100, D-galactose + C. spinosa 200) were used. Mice were administered an injection of D-galactose (100 mg/kg, subcutaneous) and orally administered C. spinosa (50, 100, or 200 mg/kg) daily for 8 weeks. RESULTS: Syringic acid was detected and the total amount was 204.629 µg/g. Addition of 0.05 mg/mL C. spinosa extract provided significant protection against the damage of DNA bands. C. spinosa attenuated D-galactose-induced learning dysfunctions in mice and significantly increased memory retention. Malondialdehyde (MDA) levels increased and superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities decreased in the D-galactose group. C. spinosa (200 mg/kg body weight) significantly decreased MDA level and increased SOD, GPx, and CAT activities. CONCLUSION: These results show that C. spinosa has the potential in ameliorating cognitive deficits induced by D-galactose in mice and the antioxidant activity may partially account for the improvement of learning and memory function.

Anticancer effect of COX-2 inhibitor DuP-697 alone and in combination with tyrosine kinase inhibitor (E7080) on colon cancer cell lines.

Colorectal cancer remains one of the most common types of cancer and a leading cause of cancer death worldwide. In this study, we aimed to investigate effects of DuP-697, an irreversible selective inhibitor of COX- 2 on colorectal cancer cells alone and in combination with a promising new multi-targeted kinase inhibitor E7080. The HT29 colorectal cancer cell line was used. Real time cell analysis (xCELLigence system) was conducted to determine effects on colorectal cell proliferation, angiogenesis was assessed with a chorioallantoic membrane model and apoptosis was determined with annexin V staining. We found that DuP-697 alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. For the antiproliferative effect the half maximum inhibition concentration (IC50) was 4.28?10-8 mol/L. Antiangiogenic scores were 1.2, 0.8 and 0.5 for 100, 10 and 1 nmol/L DuP-697 concentrations, respectively. We detected apoptosis in 52% of HT29 colorectal cancer cells after administration of 100 nmol/L DuP-697. Also in combination with the thyrosine kinase inhibitor E7080 strong antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells were observed. This study indicates that DuP-697 may be a promising agent in the treatment of colorectal cancer. Additionally the increased effects observed in the combination with thyrosine kinase inhibitor give the possibility to use lower doses of DuP-697 and E7080 which can avoid and/or minimize side effects.

Investigation of the role of the NO-cGMP pathway on YC-1 and DEA/NO effects on thoracic aorta smooth muscle responses in a rat preeclampsia model.

The present study was designed to investigate the effects of YC-1, a nitric oxide (NO)-independent soluble guanylate cyclase (sGC) activator, and DEA/NO, a NO donor, on smooth muscle responses in the preeclampsia model with suramin-treated rats and on the levels of cyclic guanosine monophosphate (cGMP) of thoracic aorta rings isolated from term-pregnant rats. Rats of 2 groups, control group and suramin group, were given intraperitoneal injection of saline or suramin, respectively. Suramin injection caused increased blood pressure, protein in urine, and fetal growth retardation. Thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction and papaverine relaxation responses were similar. Relaxation responses of YC-1 and DEA/NO decreased in suramin group. In both groups in the presence of ODQ, a sGC inhibitor, the relaxation responses of YC-1 and DEA/NO decreased. The cGMP content was determined by radioimmunoassay technique. The content of cGMP in the suramin group decreased. In the presence of YC-1 and DEA/NO in both groups, cGMP content increased, but in ODQ-added groups, there was a significant decrease. We conclude that in preeclampsia, the decrease of relaxation responses and the decrease of cGMP content could be due to the reduction in stimulation of sGC and the decrease in cGMP levels.

The effect of octreotide, an analog of somatostatin, on bleomycin-induced interstitial pulmonary fibrosis in rats.

In this study, octreotide (OCT), a synthetic somatostatin analog, was tested for its beneficial effects in the prevention of interstitial pulmonary fibrosis (IPF) induced by bleomycin (BLM) in rats by histological examination and by evaluating tissue OH-proline levels. Thirty male Wistar rats were divided randomly into three groups: group I: intratracheal (i.t.) BLM (7.5 mg/kg, single dose) + saline solution [0.9% NaCl, subcutaneously (s.c.), once-daily for 7 days]; group II: i.t. BLM (7.5 mg/kg, single dose) + OCT acetate (82.5 µg/kg, s.c., once-daily for 7 days); and the control group. At the end of the 7 days, lung tissues were excised and examined by histopathological methods. Levels of tissue hydroxyproline (OH-proline) were determined. BLM administration resulted in prominent histopathologic findings, such as diffuse alveolar damage and interstitial pulmonary fibrosis, as well as a significant increase in OH-proline level, as compared to controls. OCT application explicitly attenuated the histopathologic changes to a significant extent. OCT decreased paranchymal fibrosis and structural deformities in BLM-induced lung fibrosis. These results suggest that OCT administration to rats with BLM-induced IPF has a protective effect. Further studies are necessary to reveal the molecular mechanism(s) of OCT-induced protective effect.

The Evaluation of Microcarcinoma in Differentiated Thyroid Cancers According to Old and New TNM Classification.

OBJECTIVE: In this study, we aimed to evaluate the tumor size for proximal and distant metastases when the new and old TNM classification is taken into account in differentiated thyroid cancers. MATERIAL AND METHODS: Two hundred sixty eight patients diagnosed with thyroid carcinoma, undergoing bilateral total or subtotal thyroidectomy treated with high doses of I-131 were examined retrospectively. The data of these patients were compared after classification, according to tumor size <1 cm and <2 cm, lymph node metastases thyroid and tumor capsule invasion at the time of diagnosis, and accumulation of abnormal activity in post I-131 treatment whole-body scan. I-131 uptakes besides physiological and thyroid bed were considered as abnormal activity uptakes. RESULTS: A total of 268 patients with average age of 19-82 yrs (mean: 47.0±13.8 yrs) were included in the study. At postoperative histopathological evaluation, 228 (85.1%) of patients were reported as papillary, 13 (4.9%) as follicular, 23 (8.6%) as well differentiated tumor of unknown malignant potential, 2 (0.7%) as insular and 2 (0.7%) as Hürthle-cell carcinoma. In patients with known tumor size, 96 of 207 (46.4%) patients' tumor size was <1 cm and in 111 (53.6%) >1 cm. In the same group, according to the revised TNM classification, in 149 of 207 patients (72%) the tumor size was <2 cm, whereas in 58 (28%) >2 cm. Of 187 patients with negative lymph nodes, 15 (8%) showed abnormal activity accumulation in the first post I-131 treatment whole-body scan and 10 (40% of 25 patients) positive lymph node (p<0.05) involvement. CONCLUSION: Since the treatment of patients with microcarcinoma is controversial, tumor size should not be the only factor considered in patients with differentiated thyroid cancer Tissue tumor invasion, age, gender and multifocality should also be taken into account. CONFLICT OF INTEREST: None declared.

Evaluation of myocardial viability with thallium-201 infusion MPSPECT after oral glucose application in patients with chronic coronary artery disease.

AIM: The aim of this study was to evaluate the myocardial viability in nondiabetic patients with chronic coronary artery disease (CCAD) or past myocardial infarction (MI), using thallium-201 infusion myocardial perfusion single-photon emission computed tomography (MPSPECT) imaging after oral glucose application (Glu+Tl-infusion). MATERIALS AND METHODS: In this study, 33 nondiabetic patients (three female, 30 male, mean age: 55.24+/-11 years, range: 33-77 years) with MI history or known CCAD were included. Rest/redistribution/24 h-late-MPSPECT imaging was performed for all patients. In all patients in whom fixed perfusion defect was observed on any wall of the left ventriculi, after 24 h-late-MPSPECT imaging, 75 g oral glucose was given. Thirty minutes later, 1 mCi thallium-201 in 100 ml of physiological saline solution was applied in a period of 20 min by slow infusion. After infusion at the 10th minute, MPSPECT imaging was performed. Perfusion was evaluated visually for a total of 3432 segments with the 26-segment 5-point scoring technique. Scoring measured perfusion as 0 = no perfusion defect, 1 = mildly reduced, 2 = moderately reduced, 3 = severely reduced, and 4 = absent uptake. Scores '0 and 1' were considered normal and scores '2-4' were considered abnormal. RESULTS: For serum insulin levels measured after glucose application, a significant increase was determined, according to the period before glucose application (P<0.001). When compared with rest MPSPECT images, segmental perfusion improvement both in redistribution and in the 24 h-late-MPSPECT images were 16.3 and 18.3%, respectively. This ratio was found to be 27.2% for Glu+Tl-infusion images. The ratios of segments in which perfusion was worsening were calculated to be 9.4, 14.5, and 7.3%, respectively, for redistribution, 24 h-late-MPSPECT, and Glu+Tl-infusion images. When this evaluation was made for all three vessel areas, again the highest perfusion improvement and the lowest perfusion worsening were detected for Glu+Tl-infusion images. In addition, when this evaluation was made for the three vessel areas according to the coronary narrowing degree, again the highest perfusion improvement was detected for Glu+Tl-infusion images, in segments in the left anterior descending artery, and right coronary artery areas with >/=90% narrowing. In rest images, in segments with segmental scores of 3 and 4, when the total reversibility ratio was evaluated, this ratio was calculated to be 0.7% for redistribution images and 4.5% for 24 h-late-MPSPECT. The highest total reversibility ratio in these segments was detected with Glu+Tl-infusion images to be 10.3%. When we evaluated the patients with respect to the MI history time, the highest segmental perfusion improvement was detected in patients with 0-3 months of MI history. CONCLUSION: We conclude that in nondiabetic patients who are known to have CCAD or past MI history, Glu+Tl-infusion is an easily applicable method that gives better results for the evaluation of myocardial viability.

The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model.

The pathophysiology of pre-eclampsia is still unknown thus effective primary prevention is not possible at the stage. The present study was conducted to research the smooth muscle responses in the pre-eclampsia model with suramin treated rats and the effect of phosphodiesterase-5 (PDE5) inhibitor on these responses. Rats of three groups; control, suramin and suramin+sildenafil were given intraperitoneal injections of saline, suramin or sildenafil citrate. Suramin injections caused increased blood pressure, protein in urine and caused fetal growth retardation. The use of sildenafil citrate straightened significantly both blood pressure and average fetus weight, but did not reach to control values. At the end of pregnancy, thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction responses, sodium nitroprusside and papaverine relaxation responses were similar in three groups. Contraction responses of phenylephrine, increased significantly in suramin group. Relaxation responses of acethylcholine and bradykinin decreased in suramin group. The use of sildenafil citrate partially straightened both relaxation and contraction responses, but did not reach to control values. In all groups in the presence of L-nitromonomethylarginine (L-NAME), 1H-(1, 2, 4) oxadiazole (4, 3-a) guinoxalin-1-one (ODQ) and indomethacin decreased the relaxation responses of acetylcholine and bradykinin. The cyclic guanosine monophosphate (cGMP) content of thoracic aorta tissue was determined by radioimmunoassay technique. The content of cGMP in suramin group decreased and use of sildenafil citrate increased the cGMP content but did not reach to control values. We conclude that in pre-eclampsia, the increase of contraction responses, the decrease of relaxation responses and the decrease of cGMP content can depend on insufficiency about synthesis or release of relaxant factors which was released from the vessel endothelium. The results in this study show that in pre-eclampsia; PDE5 inhibitors enhance endothelial function and may be used for protection. Further studies are needed to clear the efficiency and safety of PDE5 inhibitors.