ABSTRACT
AIM: To explore the action of doxorubicin on vascular smooth muscle cells. METHODS: Isometric tension of denuded or intact thoracic aortic vessels was recorded and [Ca(2+)](i) in isolated aortic smooth muscle cells was measured by using Fluo-3. RESULTS: Doxorubicin induced phasic and tonic contractions in denuded vessels and increased levels of [Ca(2+)](i) in single muscle cells. Treatment with 10 micromol/L ryanodine had no effect on basal tension, but it did abolish doxorubicin-induced phasic contraction. Treatment with 10 mmol/L caffeine induced a transient phasic contraction only, and the effect was not significantly altered by ryanodine, the omission of extracellular Ca(2+) or both. Phenylephrine induced rhythmic contraction (RC) in intact vessels. Treatment with 100 micromol/L doxorubicin enhanced RC amplitude, but 1 mmol/L doxorubicin abolished RC, with an increase in maximal tension. Caffeine at 100 micromol/L increased the frequency of the RC only. In the presence of 100 micromol/L caffeine, however, 100 micromol/L doxorubicin abolished the RC and decreased its maximal tension. Treatment with 10 micromol/L ryanodine abolished the RC, with an increase in the maximal tension. In Ca(2+)-free solution, doxorubicin induced a transient [Ca(2+)](i) increase that could be abolished by ryanodine pretreatment in single muscle cells. The doxorubicin-induced increase in [Ca(2+)](i) was suppressed by nifedipine and potentiated by ryanodine and charybdotoxin. CONCLUSION: Doxorubicin not only releases Ca(2+) from the sarcoplasmic reticulum but also promotes the entry of extracellular Ca(2+) into vascular smooth muscle cells.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Calcium/metabolism , Doxorubicin/pharmacology , Muscle, Smooth, Vascular/drug effects , Aniline Compounds , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/metabolism , Fluorescent Dyes , Isometric Contraction/drug effects , Male , Mice , Mice, Inbred C57BL , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Sarcoplasmic Reticulum/drug effects , Sarcoplasmic Reticulum/metabolism , XanthenesABSTRACT
Samples of soil, vegetables, crops and air collected from Yuqiao Incineration Paint, Pudong Shanghai, were analyzed with an AMA-254 liquid/solid mercury analyzer. It is shown that background levels(BLs,2001) of mercury in surface soil is a little higher, mercury content in soils one year after operation(2002) and two year(2003) were both higher than BLs. The levels of mercury in vegetables is higher than Standard levels (GB 2762-94), the content of mercury in Soya and broomcorn sampled in 2003 was 2.3 and 2.7 times than that in 2002. Atmospheric mercury levels were 10.1, 5.0 and 10.6 ng/m3 in up-site,site and down-site.
Subject(s)
Environmental Monitoring , Environmental Pollutants/analysis , Incineration , Mercury/analysis , China , Soil/analysisABSTRACT
AIM: To investigate the changes of function of large conductance of calcium-activated potassium channels (BK(Ca) channels) in thoracic aortic smooth muscle cells in early stage of streptozotocin (STZ)-induced diabetic C57BL/6J mice. METHODS: Vascular muscle tension in the isolated thoracic aortic rings of mice was compared, and the role of BK(Ca) channels in relaxation of isolated mice thoracic aortic rings induced by acetylcholine (ACh) was determined. Meanwhile, single vascular smooth muscle cells (VSMCs) were isolated by collagenase, and BK(Ca) currents were recorded by patch-clamp single channel recording technique in symmetric high potassium solution. RESULTS: Tetraethylammonium (TEA) 1 mmol/L, a selective calcium-activated potassium channel blocker, caused significant rightward shift in the concentration-response curves of ACh in the isolated thoracic aortic rings of diabetic mice and pD2 value of ACh-induced relaxation was decreased notably after TEA treatment [(6.3+/-0.4) vs (6.9+/-0.5), n=10 rings from 7 mice, P<0.01]. But pD2 value of ACh-induced relaxation in age-matched control mice did not change in presence and absence of TEA 1 mmol/L [(6.4+/-0.15) vs (6.5+/-0.5), n=7 rings from 6 mice, P>0.05]. Furthermore, conductance of BK(Ca) channels in single thoracic aortic smooth muscle cells was decreased [(199+/-15) pS, n=10 cells from 7 mice vs (266+/-11) pS, n=12 cells from 6 mice, P<0.01], but probability of open of BKCa channels was increased [(0.51+/-0.28) vs (0.11+/-0.06), n=6 cells from 6 mice, P<0.01], and the mean closed time in diabetic mice was reduced [(15+/-15) vs (132+/-98), n=6 cells from 6 mice, P<0.05]. CONCLUSION: The opening of BK(Ca) channels was increased in thoracic aortic smooth muscle cells in the early stage of STZ-induced diabetic C57BL/6J mice by reducing mean closed time, but the conductance of BK(Ca) channels was decreased.
