Scutellarin attenuates endothelium-dependent aasodilation impairment induced by hypoxia reoxygenation, through regulating the PKG signaling pathway in rat coronary artery

Scutellarin(SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we investigated the vasoprotective effects of SCU against HR-induced endothelial dysfunction(ED) in isolated rat CA and the possible mechanisms involving cyclic guanosine monophosphate(c GMP) dependent protein kinase(PKG). The isolated endothelium-intact and endothelium-denuded rat CA rings were treated with HR injury. Evaluation of endothelium-dependent and-independent vasodilation relaxation of the CA rings were performed using wire myography and the protein expressions were assayed by Western blotting. SCU(10–1 000 μmol·L-1) could relax the endothelium-intact CA rings but not endothelium-denuded ones. In the intact CA rings, the PKG inhibitor, Rp-8-Br-c GMPS(PKGI-rp, 4 μmol·L-1), significantly blocked SCU(10–1 000 μmol·L-1)-induced relaxation. The NO synthase(NOS) inhibitor, NO-nitro-L-arginine methylester(L-NAME, 100 μmol·L-1), did not significantly change the effects of SCU(10–1 000 μmol·L-1). HR treatment significantly impaired ACh-induced relaxation, which was reversed by pre-incubation with SCU(500 μmol·L-1), while HR treatment did not altered NTG-induced vasodilation. PKGI-rp(4 μmol·L-1) blocked the protective effects of SCU in HR-treated CA rings. Additionally, HR treatment reduced phosphorylated vasodilator-stimulated phosphoprotein(p-VASP,phosphorylated product of PKG), which was reversed by SCU pre-incubation, suggesting that SCU activated PKG phosphorylation against HR injury. SCU induces CA vasodilation in an endothelium-dependent manner to and repairs HR-induced impairment via activation of PKG signaling pathway.

Developmental- and food-dependent foraging transcript levels in the desert locust

Drastic changes in the environment during a lifetime require developmental and physiological flexibility to ensure animal survival. Desert locusts, Schistocerca gregaria, live in an extremely changeable environment, which alternates between periods of rainfall and abundant food and periods of drought and starvation. In order to survive, locusts display an extreme form ofphenotypic plasticity that allows them to rapidly cope with these changing conditions by converting from a cryptic solitarious phase to a swarming, voracious gregarious phase. To accomplish this, locusts possess different conserved mediators of phenotypic plasticity. Recently, attention has been drawn to the possible roles of protein kinases in this process. In addition to cyclic AMP-dependent protein kinase （PKA）, also cyclic GMP-dependent protein kinase （PKG）, which was shown to be involved in changes of food-related behavior in a variety of insects, has been associated with locust phenotypic plasticity. In this article, we study the transcript levels of the S. gregaria orthologue of the foraging gene that encodes a PKG in different food-related, developmental and crowding conditions. Transcript levels of the S. gregariaforaging orthologue are highest in different parts of the gut and differ between isolated and crowd-reared locusts. They change when the availability of food is altered, display a distinct pattern with higher levels after a moult and decrease with age during postembryonic development.

Shunxin decoction(顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction induced by abdominal aorta constriction through cyclic guanosine monophosphate-dependent protein kinase Signaling Pathway

OBJECTIVE: To determine whether Shunxin decoction(顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction(HFp EF) by regulating the cyclic guanosine monophosphatedependent protein kinase(c GMP-PKG) signaling pathway. METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFp EF rat models using the abdominal aorta constriction method. These rats in the HFp EF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin lowdose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, lowdose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide(NT-pro BNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the c GMP-PKG pathway. Natriuretic peptide receptor A(NPRA) and guanylate cyclase(GC) were detected by immunohistochemistry, and e NOS, phosphodiesterase 5A(PDE5A), and c GMP-dependent protein kinase 1(PKG I) were determined by Western blotting. RESULTS: Compared to the model group, the thickness of the interventricular septum at the end of diastole(IVSd) and the thickness of the posterior wall at the end of diastole(PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced(P < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased(P < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group(P < 0.01). Compared to the model group, the expressions of e NOS and PKG I increased(P < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group(P < 0.01). CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFp EF. It increases the expression of NPRA, GC, and e NOS in the myocardial cell c GMP-PKG signaling pathway, upregulates c GMP expression, decreases PDE5A expression to reduce the c GMP degradation. Thus, the c GMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFp EF rats.