gyy-4137 and Hypertension

Previous studies demonstrated that H. In this study, GYY4137 (a H. Our results showed that GYY4137 normalized the SBP (P < 0.0001), increased EDR (P < 0.01), reduced oxidative stress (increased the content of SOD and reduced the content of MDA) of SHR. Meanwhile, GYY4137 could promote the proliferation (P < 0.01) and migration (P < 0.01) of HUVECs, increase the expression of endothelial NO synthase (eNOS) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) both in SHR and HUVECs treated with GYY4137. In addition to the above results, the PIP3/Akt signaling pathway was activated and the expression of caspase 3 was increased by GYY4137. However, all the above effects of GYY4137 were blocked by ZD6474 (a VEGFR2 inhibitor).. GYY4137 had a hypotensive and vascular protect effect on PH. This effect might be mediated through upregulating the expression of VEGFR2, which subsequently alleviating oxidant-provoked vascular endothelial dysfunction, and promoting the proliferation and migration of endothelial cells in SHR.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Sulfide; Hypertension; Male; Malondialdehyde; Morpholines; Organothiophosphorus Compounds; Oxidative Stress; Protective Agents; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Signal Transduction; Superoxide Dismutase; Vascular Endothelial Growth Factor A

Hydrogen sulfide (H

Topics: Animals; Antihypertensive Agents; Aorta, Thoracic; Female; Fetal Growth Retardation; Fetus; Hydrogen Sulfide; Hypertension; Litter Size; Malondialdehyde; Morpholines; Organothiophosphorus Compounds; Placenta; Pregnancy; Rats, Wistar; Sulfides

Stroke-prone spontaneously hypertensive rats (SHRSP/Izm; SHRSP) develop severe hypertension and die of cerebral stroke. However, the genetic mechanisms underlying their stroke susceptibility have not been clarified yet. In this study, we used astrocytes from the newborn brain cortex of spontaneously hypertensive rats (SHR/Izm; SHR) and SHRSP to find the difference of genetic characteristics. Astrocytes are known to have functions of vasodilation and nutrient uptake for neurons in the brain. The continuous generation of hydrogen peroxide (H

Topics: Animals; Astrocytes; Brain; Cell Survival; Cells, Cultured; Cystathionine beta-Synthase; Glucose Oxidase; Glutathione; Glutathione Disulfide; Hydrogen Peroxide; Hydrogen Sulfide; Hypertension; Morpholines; Organothiophosphorus Compounds; Oxidative Stress; Rats, Inbred SHR; Stroke; Sulfur

The exact etiology of preeclampsia is unknown, but there is growing evidence of an imbalance in angiogenic growth factors and abnormal placentation. Hydrogen sulfide (H2S), a gaseous messenger produced mainly by cystathionine γ-lyase (CSE), is a proangiogenic vasodilator. We hypothesized that a reduction in CSE activity may alter the angiogenic balance in pregnancy and induce abnormal placentation and maternal hypertension.. Plasma levels of H2S were significantly decreased in women with preeclampsia (P<0.01), which was associated with reduced placental CSE expression as determined by real-time polymerase chain reaction and immunohistochemistry. Inhibition of CSE activity by DL-propargylglycine reduced placental growth factorproduction from first-trimester (8-12 weeks gestation) human placental explants and inhibited trophoblast invasion in vitro. Knockdown of CSE in human umbilical vein endothelial cells by small-interfering RNA increased the release of soluble fms-like tyrosine kinase-1 and soluble endoglin, as assessed by enzyme-linked immunosorbent assay, whereas adenoviral-mediated CSE overexpression in human umbilical vein endothelial cells inhibited their release. Administration of DL-propargylglycine to pregnant mice induced hypertension and liver damage, promoted abnormal labyrinth vascularization in the placenta, and decreased fetal growth. Finally, a slow-releasing H2S-generating compound, GYY4137, inhibited circulating soluble fms-like tyrosine kinase-1 and soluble endoglin levels and restored fetal growth in mice that was compromised by DL-propargylglycine treatment, demonstrating that the effect of CSE inhibitor was attributable to inhibition of H2S production.. These results imply that endogenous H2S is required for healthy placental vasculature and that a decrease in CSE/H2S activity may contribute to the pathogenesis of preeclampsia.

Topics: Adolescent; Adult; Alkynes; Animals; Antigens, CD; Cells, Cultured; Cystathionine gamma-Lyase; Disease Models, Animal; Endoglin; Endothelium, Vascular; Female; Fetal Development; Glycine; Humans; Hydrogen Sulfide; Hypertension; Mice; Mice, Inbred C57BL; Morpholines; Neovascularization, Physiologic; Organ Culture Techniques; Organothiophosphorus Compounds; Placenta; Placenta Diseases; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Proteins; Pregnancy, Animal; Receptors, Cell Surface; Vascular Endothelial Growth Factor Receptor-1; Young Adult