Amiloride attenuates hypoxia-induced proliferation of rats pulmonary artery smooth muscle cells by suppressing Na+/ H+ exchanger-1 / 中国应用生理学杂志

<p><b>AIM</b>To study the influence of Na+/H+ exchange inhibitor amiloride on hypoxia-induced proliferation in rats pulmonary artery smooth muscle cells (PASMCs), also observe the change of Na+/H+ exchanger-1 (NHE-1) activity and expression.</p><p><b>METHODS</b>Rats PASMGs were cultured in normoxia (21% O2) or hypoxia (2%O2) for 24 hours, as well as administered amiloride with various concentrations, cultured for 24 hours, then determined MTT OD values and rates of PCNA positive cells to investigate cells proliferation, moreover intracellular pH was determined by interactive Laser Cytometer, and Na+/H+ exchanger-1 mRNA expression was determined by RT-PCR.</p><p><b>RESULTS</b>Hypoxic exposure heightened intracellular pH and mRNA expression of NHE-1 in PASMCs, however, 3.123-50 micromol/L amiloride depressed them gradually. Additionally, hypoxic exposure raised MTT OD value and rates of PCNA positive cells, similarly, the above two indexes descended gradually with presence of 3.125-50 micromol/L amiloride.</p><p><b>CONCLUSION</b>Na+/H+ exchange inhibitor amiloride can suppress hypoxia-induced proliferation in pulmonary artery smooth muscle cells, which is due to depress activity and expression of NHE-1.</p>

Study on relativity of hypoxic pulmonary hypertension with levels of endothelin-1 and vascular endothelial growth factor in plasma of pulmonary artery and carotid artery / 中国应用生理学杂志

<p><b>AIM</b>To study the effects of endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) on the mechanism of hypoxic pulmonary hypertension (HPH).</p><p><b>METHODS</b>We studied 4 groups of age-controlled male rats, i.e., normal control for 2 weeks group (N2), normal control for 3 weeks group (N3), exposed to hypoxia for 2 weeks group (H2) and for 3 weeks group (H3). Chronic HPH rat models were established by chronic hypobaric hypoxia [(10.0% +/- 0.5% O2] for 2 and 3 weeks, respectively. The rats were anesthetized and fixed, and the levels of mean pulmonary artery pressure (mPAP) and carotid arterial pressure (CAP) were measured using catheters by a microcomputer via transducers. The weight ratio of right ventricle (RV) and left ventricle and septum (LV + S) [RV/ (LV+S)] were determined. The contents of ET-1 in plasma of pulmonary artery and carotid artery and in homogenates of lung and systemic arteries were determined by radioimmunoassay, and the contents of VEGF in serum of pulmonary artery and carotid artery were determined by ABC-ELISA.</p><p><b>RESULTS</b>HPH rat models were established successfully. Compared with control groups, the values of ET-1 were both enhanced in carotid artery and pulmonary artery plasma in model groups (P < 0.01). In the HPH groups, the level of pulmonary artery plasma ET-1 was significantly lower than that of carotid artery plasma, but just the reverse was ET-1 in control rats. The levels of ET-1 in homogenates of lungs from HPH models were significantly higher than those in homogenates of lungs from control groups (P < 0.01), and markedly higher than those in homogenates of systemic arteries from HPH rats (P < 0.01) SThe values of VEGF in serum of pulmonary artery from H3 group were significantly higher than those from control groups and H2 group (P < 0.01). In serum of carotid artery, the values of VEGF from the HPH models were higher than those from the control groups (P < 0.01).</p><p><b>CONCLUSION</b>ET-1 and VEGF play important roles in the pathogenesis of HPH. The result that ET-1 concentration around pulmonary arteries was significantly higher than that around systemic arteries may be one of the mechanisms accounting for the different reaction of them to hypoxia.</p>

Pulmonary artery in endotoxemia rat. Effects of atrial natriuretic peptide on relaxation and constriction of aorta and pulmonary artery in endotoxemia rat / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of atrial natriuretic peptide(ANP) on constriction and relaxation of pulmonary artery and aorta in endotoxemia rat in vitro.</p><p><b>METHODS</b>24 male SD rats were randomly divided into 3 groups, control group, LPS group, ANP therapy group. These groups were injected physiologic salt water, lipopolysaccharide (LPS 2 mg/kg) and LPS + ANP(LPS 2 mg/kg, ANP 2 microg/kg) into vein respectively. After 4 hours, rats were exsanguinated to kill and aorta and pulmonary artery were separated from heart-lung for experiment of blood vessel rings. Constriction effects of aorta and pulmonary artery by norepinephrine (NE), relaxation of aorta and pulmonary artery by acetylcholine (ACh) and sodium nitroprusside SNP) observed by perfusion system in vitro.</p><p><b>RESULTS</b>Sensitiveness of NE-induced (10(-9)-10(-7) mol/L) constriction of aorta in LPS group was attenuated and EC50 was increased, but its strength (3 x 10(-7)-10(-6) mol/L) was greater comparing with control group (P < 0.01). In ANP group, the NE-induced contractility of aorta was similar to LPS group (P > 0.05). Comparing with control group, NE-induced constriction of pulmonary artery exposure to LPS was reinforced especially in 3 x 10(-7)-10(-6) mol/L of NE (P < 0.01), but its EC50 was obviously higher (P <0.05). There was no significant difference between ANP group and control group in constriction of pulmonary artery (P > 0.05). Relaxation and sensitiveness of aorta and pulmonary artery exposure to LPS were evidently improved in ANP therapy group induced by ACh and SNP respectively (P < 0.01, P < 0.05) and their EC50 markedly decreased comparing with LPS group (P < 0.01, P < 0.05) respectively.</p><p><b>CONCLUSION</b>ANP can suppress the reinforcing of NE-induced constriction of pulmonary artery exposure to LPS and partly or entirely reverse the attenuated relaxation of pulmonary artery and aorta induced by ACh and SNP in endotoxemia rats.</p>

Study on the mechanism of how vasonatrin peptide can attenuate the growth-promoting effect of hypoxia in cardiac fibroblasts / 中国应用生理学杂志

<p><b>AIM</b>To investigate how vasonatrin peptide (VNP) can attenuate the growth-promoting effect of hypoxia in cardiac fibroblasts cultured from neonatal rats.</p><p><b>METHODS</b>The cultured cardiac fibroblasts were divided randomly into four groups: control group, hypoxia group, hypoxia + VNP group and hypoxia + 8-Bromo-cGMP group. The growth of cardiac myocytes was measured by the means of MTT method. The effect of VNP on the intracellular level of cGMP and PCNA were measured by the means of radioimmunoassay and immunohistochemistry stain respectively.</p><p><b>RESULTS</b>Hypoxia (24 h) significantly increased the MTT A490nm value of cardiac fibroblasts (P < 0.05 vs control group). Both VNP (10(-7) mol/L) and 8-Bromo-cGMP (10(-3) mol/L) decreased MTT A490 nm value in cardiac fibroblast (P < 0.05 vs hypoxia group). VNP (10(-7) mol/L) increased the intracellular level of cGMP (P < 0.05 vs control and hypoxia group). Hypoxia (24 h) significantly increased the expression of proliferating cell nuclear antigen (PCNA) in cardiac myocytes (P < 0.05, vs control group), but VNP (10(-7) mol/L) decreased it.</p><p><b>CONCLUSION</b>VNP can attenuate hypoxia-induced growth-promoting effect in cardiac fibroblasts which is associated with the changes of cGMP and PCNA.</p>

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).