Vasorelaxing effect of idoxifene on human internal mammary arteries / 生理学报

The purpose of this study was to investigate the vasorelaxing effect and mechanism of idoxifene (a new estrogen receptor modulator) on human internal mammary artery (HIMA). HIMA segments were harvested from men during coronary artery bypass grafting surgery. Patients with diabetes mellitus, hypercholesterolemia, hypertension, or smoking habit were excluded. The vasorelaxing effect of idoxifene on artery rings from HIMA with and without endothelium was measured by means of perfusion in vitro. Cumulative dose-response to idoxifene in the range of 0.01-10 micromol/L was observed in the presence and absence of NO synthase inhibitor L-NAME. It was also studied whether the vasodilation effect of idoxifene on HIMA was blocked by methylene blue (MB), an inhibitor of guanylate cyclase (GC). The results obtained from idoxifene were compared with those from 17beta-estradiol (E(2)). It was found that idoxifene caused a concentration-dependent relaxation on HIMA. The dose range was from 0.03 micromol/L (minimal vasodilatory concentration) to 3 mmol/L (maximal vasodilatory concentration). It was also found that the vasorelaxation effect of idoxifene on HIMA was dependent on endothelium. E(2) (0.1-100 micromol/L) also resulted in an endothelium-dependent vasorelaxation, but the vessels were 15-fold less sensitive to E(2) than to idoxifene in their vasorelaxation responses. The EC(50) for E(2) was 4.65+/-0.34 micromol/L, compared with 0.32+/-0.02 micromol/L for idoxifene. The mean maximal vasodilatory value of E(2) was 88.3+/-5.7%, compared with 88.6+/-7.2% for idoxifene. Pretreatment with L-NAME (100micromol/L) abolished idoxifene-induced vasodilation virtually by blocking nitric oxide production. The vasorelaxing effect of idoxifene disappeared in the presence of MB (10 micromol/L). These findings demonstrate that idoxifene results in an endothelium-dependent vasorelaxation of HIMA, like estrogen. The effect of idoxifene is more potent than that of traditional estrogen, and is possibly mediated by NO-GC-cGMP pathway.

Predominant Th2-type response during normal pregnancy of rats / 生理学报

The immunological parameters were analyzed during pregnancy of Lewis rats by the methods of flow cytometry, thymidine incorporation and enzyme-linked immunospot (ELISPOT). MHC II of spleen mononuclear cells (MNCs) and CD11c of periphery blood MNCs was apparently downregulated in late pregnancy, while the costimulatory molecules B7-1 and B7-2 showed no difference. Increased expression of Th2 cytokines (IL-10, IL-4) and TGFbeta was detected in the spleen and peripheral blood MNCs in the third trimester by flow cytometry. No suppression of Th1 cytokine represented by IFNgamma was found. Furthermore, antigen specific proliferation of spleen and peripheral blood MNCs was unchanged, but higher proliferation of MNCs from mesenteric lymph nodes was shown in late pregnancy. There was an inhibition of antigen specific antibody production in pregnancy examined by ELISPOT. These data indicate the immunomodulatory effects of sex-hormones in pregnancy, which may be related to the remission of T cell-mediated autoimmune diseases during pregnancy.

Vasorelaxing role of vasonatrin peptide in human intramammary artery in vitro / 生理学报

The purpose of this study was to investigate the vasorelaxing effect of vasonatrin peptide (VNP) on human intramammary artery (HIMA).The vasorelaxing effect of VNP on HIMA was measured by means of perfusion in vitro. The effects of HS-142-1, TEA, 8-Br-cGMP and methylene blue (MB) were also observed. It was found that VNP caused a concentration-dependent relaxation in HIMA which was independent of the endothelium. 8-Br-cGMP (0.1-1000 micromol/L) also caused a concentration-dependent relaxation in HIMA. The vasorelaxing effect of VNP disappeared in the presence of HS-142-1 (20 micromol/L), an antagonist of the natriuretic peptide guanylate cyclase (GC) receptor. MB (10 micromol/L), an inhibitor of GC, not only blocked completely the relaxation of HIMA, but also enhanced the vascular contraction induced by norepinephrine. TEA (1 mmol/L), an antagonist of calcium activated potassium channels (K(Ca)), reduced but not completely blocked the vasorelaxing effect of VNP. These findings suggest that VNP can relax HIMA, which is independent of the endothelium. This effect is possibly achieved by the binding of VNP with the natriuretic peptide GC receptors in the smooth muscle cells (SMCs), leading to an increase in intracellular cGMP level. Moreover, the vasorelaxing effect of VNP is associated with K(Ca).