vardenafil-dihydrochloride and Ischemia

The purpose of the study is to evaluate the effect of vardenafil on the histopathology and biochemical parameters in reducing damage in experimental ovarian ischemia and ischemia/reperfusion injury in a rat model and to compare the effect of two different doses of vardenafil.. Forty-two rats with experimental ovarian torsion. Group-I: sham; Group-II: ovarian ischemia; Group-III: 2 hours of ischemia followed by a 2-hour reperfusion. Group-IV: two hours before the sham operation, rats received 1mg/kg vardenafil; Group V and VI: A 2-hour period of ovarian ischemia was applied, in which rats were treated with intraperitoneal vardenafil 1 and 2mg/kg dose, after 1.5 hours of ovarian ischemia. After 2 hours of reperfusion, the ovaries on the right side were removed for examination. The ovarian ischemia/reperfusion injury was evaluated by calculating total antioxidant status, total oxidant status and oxidative stress index; and histopathologic examination of all ovarian rat tissue.. The histologic findings in vardenafil treatment groups were statistically significant decreased edema and follicle degeneration, with vascular congestion, hemorrhage and follicle degeneration being dose-dependent. There were no statistically significant changes in the biochemical parameters.. According to histopathological examination, low and high dose vardenafil is effective in attenuating ischemia-reperfusion induced ovary injury.

Topics: Animals; Antioxidants; Female; Ischemia; Ovarian Diseases; Ovary; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Torsion Abnormality; Vardenafil Dihydrochloride; Vasodilator Agents

To investigate the effect of vardenafil in kidney of rats submitted to acute ischemia and reperfusion.. Twenty-eight rats were randomly distributed into two groups. Right nephrectomy was performed and the vardenafil group received vardenafil solution (at a concentration of 1 mg/ml in 10 mg/kg) while the control group received 0.9% saline solution (SS) one hour prior to the ligature of the left renal pedicle. After one hour of ischemia, animals were submitted to twenty-four hours of reperfusion, followed by left nephrectomy. The kidney's histological parameters evaluated on the study included vacuolar degeneration and tubular necrosis. Apoptosis was assessed by immunohistochemistry for cleaved caspase-3 using the point-counting and digital methods (Cytophotometry). Also, a biochemical analysis for creatinine was conducted.. There were statistically significant differences between groups only with regards to the vacuolar degeneration parameter and to the cleaved caspase-3 digital method.. Vardenafil showed a protective effect on the kidney of rats subjected to acute ischemia and reperfusion in this model.

Topics: Animals; Apoptosis; Caspase 3; Disease Models, Animal; Imidazoles; Immunohistochemistry; Ischemia; Kidney; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Random Allocation; Rats, Wistar; Reperfusion Injury; Reproducibility of Results; Sulfones; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

We examined whether phosphodiesterase-5 (PDE5) inhibition can promote ischemia-induced angiogenesis.. Unilateral hindlimb ischemia was generated by resecting right femoral artery in wild-type C3H/He mice, treated with either vehicle or a PDE5 inhibitor vardenafil (10 mg/kg per day). Four weeks after surgery, vardenafil significantly enhanced blood flow recovery and augmented capillary collateral formation in ischemic muscle (blood flow ratios of ischemic/nonischemic leg: 0.52+/-0.17 [vehicle] versus 0.92+/-0.09 [vardenafil], P<0.01). Vardenafil upregulated protein expression of vascular endothelial growth factor and hypoxia-inducible factor (HIF)-1 alpha in ischemic muscle and enhanced mobilization of Sca-1/Flk-1-positive endothelial progenitor cells (EPCs) in peripheral blood and bone marrow, contributing to neovascularization. Vardenafil also promoted capillary-like tube formation of human umbilical vein endothelial cells and increased the number of human blood mononuclear cell-derived EPCs in vitro. Furthermore, reporter assays showed that vardenafil and cGMP activated the transactivation activity of HIF-1 under hypoxia. These effects of vardenafil were markedly inhibited by genetic ablation of endothelial nitric oxide synthase, a soluble guanylate cyclase inhibitor, and a protein kinase G inhibitor, respectively.. Our results suggest that PDE5 inhibition enhances ischemia-induced angiogenesis with mobilization of EPCs through a protein kinase G-dependent HIF-1/vascular endothelial growth factor pathway. PDE5 inhibition may have a therapeutic potential to treat ischemic cardiovascular diseases.

Topics: Angiogenesis Inducing Agents; Animals; Capillaries; Cell Hypoxia; Cell Movement; Cells, Cultured; Collateral Circulation; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Cyclic Nucleotide Phosphodiesterases, Type 5; Disease Models, Animal; Endothelial Cells; Green Fluorescent Proteins; Hindlimb; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Imidazoles; Ischemia; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Muscle, Skeletal; Neovascularization, Physiologic; Nitric Oxide Synthase Type III; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Recovery of Function; Regional Blood Flow; RNA Interference; Signal Transduction; Stem Cells; Sulfones; Time Factors; Transfection; Triazines; Vardenafil Dihydrochloride; Vascular Endothelial Growth Factor A