Abstract:Aim To explore the effect of phenylephrine(PE,α1-adrenergic receptor agonist) on myocardial fibrosis induced by abdominal aorta coarctation (AAC) in mice and to elucidate related mechanism. Methods In this study,mice model of myocardial fibrosis were established by abdominal aorta coarctation in 28 mice, and 14 mice were randomly taken as control group and sham group. Eight weeks after surgery, mice were divided into 4 groups:AAC group, AAC+PE group (phenylephrine 0.65 mg/(kg·d) intraperitoneal injection),AAC+ Praz group (prazosin 5 mg/(kg·d) gavage) and AAC+Prop group(propranolol 10 mg/(kg·d) gavage). After administrated therapy for 4 weeks, the morphological changes of cardiac tissue were observed by hematoxylin-eosin (HE) staining, collagen volume fractions (CVF) of left ventricle were observed by Van-Gieson (VG) staining and hydroxyproline concentration were studied. The protein content of collagenⅠand collagen Ⅲ were examined by immunohistochemical analysis. Western blot was used to measure the myocardial protein expression of α-smooth muscle actin(α-SMA), transforming growth factor-β1 (TGF-β1), phosphor-drosophila mothers against decapentaplegic protein 2 (p-Smad2) and phosphor-drosophila mothers against decapentaplegic protein 3 (p-Smad3). Results Compared with control group, the heart of AAC group were developed fibrosis obviously. The CVF level and myocardial hydroxyproline concentration was significantly higher in AAC group as the same as protein level of collagenⅠand collagen Ⅲ (all P<0.01), and the protein expressions of α-SMA, TGF-β1, p-Smad2 and p-Smad3 were also elevated (all P<0.01). PE treatment significantly reduced the CVF, hydroxyproline concentration, decreased expression of collagenⅠand collagen Ⅲ and expressions of α-SMA ,TGF-β1, p-Smad2 and p-Smad3 in myocardial tissue compared with the AAC group (all P<0.05) as the same as propranolol treatment. However, prazosin had no effect on protein levels of α-SMA, TGF-β1, and p-Smad3, although a small reduction in p-Smad2 levels was observed. Conclusion These data suggest that phenylephrine was as effective as propranolol to attenuate myocardial fibrosis induced by coarctation of abdominal aorta in mice, which may be associated with suppressing the TGF-β1/Smads signal pathways.

Abstract:Aim To research the cross regulation of cGMP-dependent protein kinase(PKG) and calcineurin(CaN) in vascular smooth muscle cells(SMC) proliferation. Methods Primary vascular SMC from rat aorta were used as the experimental model.Expression of CaN and PKG was assayed using immunoblotting.Cell growth was determined by MTT assay. Results The results showed that phenylephrine(PE)-induced expression and activity of CaN protein was reduced by S-nitroso-N-acetylpenicillamine(SNAP) and Sp-8-pCPT-cGMP,but increased by Rp-8-pCPT-cGMP.The OD ratio of PKG Iα mRNA expression in 0.5 mg/L cyclosporin A(CsA) group resembled control group while in 5 mg/L CsA group was significantly higher than control group(p<0.01).Although the result of 5 mg/L CsA+10 μmol/L PE group was lower than 5 mg/L CsA group(the expression of mRNA decreased 32.2%;the production of PKG Iα protein decreased 36.7%,p<0.01),but still higher than control group obviously(p<0.05).In SMC pretreated with CsA,absorbance of cells stimulated by PE decreased by 36.67%,but it could not be further altered by the additional treatment of SNAP,Sp-8-pCPT-cGMP and Rp-8-pCPT-cGMP. Conclusion PKG and CaN can cross-regulate in vascular smooth mucle cells proliferation.

Abstract:Aim To study the effects of neferine (Nef) on constraction of the rabbit basilaris arteria Induced by phenylephrine (Phe). Methods The blood vessel tension responses to drug were measured by rabbit basilaris arteria rings (RBAR) endothelium being removed and intact endothelium in vitro. Results The RBAR precontracted with Phe can be relaxed by Nef with a significant difference from saline control group (p<0.001). The vasodilatation of Nef was not significantly differences between the endothelium removed and intact endothelium groups (p>0.05). Conclusions The RBAR precontracted with Phe can be relaxed by Nef in vitro. The vasodilatation of Nef is independent of endothelium.

Abstract:Aim The effects of melittin (a polypeptide from bee venom) on rat aorta and the relation with Ca 2+ influx were studied in this article. Methods The contractile test of the isolated aorta rings and the assay method of 45 ?Ca influx were used. Results In endothelium-intact aorta rings, melittin did not influence the rapid contractions induced by phenylephrine (PHE), but could inhibit the continuing contractions in the concentration dependent manner. In endothelium-denuded aorta rings,melittin did not have the effect on the contractile responses induced by PHE. Melittin did not cause the contraction in endothelium-intact aorta rings, but induced significantly contractions and increased the 45 ?Ca influx in endothelium-denuded aorta rings, these effects were partially antagonised by cartopril and bepridil respectively. Conclusions Melittin could cause the endothelium dependent relaxations to vascular smooth muscle, and the releasing renin and Na + - Ca 2+ exchange system could play partial role in the contractions of the endothelium-denuded vascular.