BACKGROUND

1
?????????????????????
??? ? ? ??? ? ? ??? ? ? ???
??? ? ? ( ???????????0301 )

• ???? ? ? ??
• ??? ? ?
• ( ???????????? )

2
BACKGROUND

• ???????????,?????????????????????????????????1985?
  ,??????(WHO)???????????????????????????
• ?????????????????????????????????????????????
• ???,?????????????????,?????????????????????????

3
BACKGROUND

• ?????????????????,?????,????????????????????,?????
  ????????? ????????,?????????????????????????
• ????,???????????NO???????????????,??,?????????????
  ????????????????,?????????????????????????????????
  ???????????,????????????????????????????????
• ?????,???????????,??????,????????????????????????
  ????????????,??????????????

4
BACKGROUND

• ??,???????????????,???????????????????????????????
  ?????????????,?????????????????,??????????????????
  ???????????,????????????????????????????,?????????
  ??????
• ??,????organ bath??,?????????????,????????????????
  ????????????,???????????????????????

5
OBJECTIVE

• ???????????????????????or???
• ?????????????????
• ?????????????????? ????????????????? ?Ryanodine
  ???IP3???

6
METHODS

• SD??

organ bath??
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METHODS
?? ???PE?KCl?????????????

• ???????? ??????? ? ???K-H? ? ???????? ? ??? 3?4
  mm??8???? ? ???K-H????? ? ???????????(3, 1, 1.5,
  2, 2.5, 3, 3.5, 4 g) ? ??60 min?

8
METHODS

• ??????
• KCl??? ?????0.06mol/L KCl
  ,????????,??3??
• ???? ?????10-6 mol/L??????(PE) ?
  ???? ? ?????10-5 mol/L?????(ACh) ?
  ?????????????50(50??????????????) ? ???

9
METHODS

• ????
• ???PE?KCl?????????????????
• ???PE?KCl????????????????

10
METHODS

• ?? ???CaCl2???????
• ???????? ??????????,??????3 g(?????),?????
• ?????? ???
• ????
• ????K-H?? ? ??3(??????)?? ? ??30 min
  ? ????K-H?? ? ?????0.06 mol/L KCl??????10-6
  mol/L??????(PE)?????????? ? ??5
  min????CaCl2(0.255 mmol/L) ? ???????????
• (???)

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METHODS
KCl??
KCl??
PE??
PE??
??K-H???
??K-H???
??K-H???
??K-H???
?????3??
?????3??
30 min?
30 min?
??30 min
??30 min
????K-H?
????K-H?
????K-H?
????K-H?
?? KCl (0.06 mol/L)
?? KCl (0.06 mol/L)
?? PE (10-6 mol/L )
?? PE (10-6 mol/L )
?????
?????
?????
?????
??5 min???? CaCl2(0.25-5 mmol/L)
??5 min???? CaCl2(0.25-5 mmol/L)
??5 min???? CaCl2(0.25-5 mmol/L)
??5 min???? CaCl2(0.25-5 mmol/L)
?????????
?????????
?????????
?????????
12
METHODS

• ?? ????(verapamil, Ver)??????
• ???????????
• ???????? ??????????,??????3 g(?????),?????
• ?????? ???

13
METHODS

• ????(???)
• (1)Ver???????????,??10-6
  mol/L?L???????????(Ver),??30 min?,??,??PE(10-6
  mol/L)??????,???????????20 min?
• (2)Ver?????????????,??10-6
  mol/L?Ver,??30 min?,??,??PE(10-6
  mol/L)??????,??????3?? ,???20 min,???????????
• (3)VerRR?????????????,??10-6
  mol/L?Ver,5 min?,??10-5 mol/L?ryanodine???????(rut
  henium red, RR),???25 min?,??,??PE(10-6
  mol/L)??????,??????3?????20 min,???????????
• (4)VerHP?????????????,??10-6
  mol/L?Ver,5 min?,??50 mg/L?IP3???????(heparin,
  HP),???25 min?,??,??PE(10-6 mol/L)??????,??????3?
  ? ???20 min,???????????

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METHODS
Ver (10-6 mol/L) 30 min
PE (10-6 mol/L) 30 min
Ver?
?? (3) 20 min
Ver???
?? (3) 20 min
RR 10-5mol/L
VerRR???
5 min
??10 min
?? (3) 20 min
HP 50mg/L
VerHP???
5 min
??10 min
15
RESULTS

• ?????KCl?????????????

Fig. 1A. Concentration-dependent effect of
ethanol (0.1-3) in 610-2 M KCl precontracted
rat aortic rings with endothelium at different
resting tension (1 g-4 g). Data are expressed as
Mean SD (n3-5). Plt0.05, vs. Control-3 g.
16
RESULTS
Fig. 1B. Concentration-dependent effect of
ethanol (0.1-3) in 610-2 M KCl precontracted
rat aortic rings without endothelium at different
resting tension (1 g-4 g). Data are expressed as
Mean SD (n3-5). Plt0.05, vs. Control-3 g.
17
RESULTS

• ?????PE?????????????

Fig. 2A. Concentration-dependent effect of
ethanol (0.1-3) in 10-6 M PE precontracted rat
aortic rings with endothelium at different
resting tension (1 g-4 g).Data are expressed as
Mean SD (n3-6).
18
RESULTS
Fig. 2B. Concentration-dependent effect of
ethanol (0.1-3) in 10-6 M PE precontracted rat
aortic rings without endothelium at different
resting tension (1 g-4 g).Data are expressed as
Mean SD (n3-6). Plt0.05, Plt0.01, vs.
Control-3 g.
19
RESULTS

• ?? ???CaCl2???????

Fig. 3A. Effect of ethanol at 3 on the Ca2
(2.5?10-4-5?10-3 M)-induced contraction of rat
aortic rings (the rest tension was 3 g) without
endothelium pretreated with 610-2 M KCl. Data
are expressed as Mean SD (n5-6). P lt0.05,
P lt0.01, vs. Control.
20
RESULTS
Fig. 3B. Effect of ethanol at 3 on the Ca2
(2.5?10-4-5?10-3 M)-induced contraction of rat
aortic rings (the rest tension was 3 g) without
endothelium pretreated with 10-6 M PE. Data are
expressed as Mean SD (n5-6). P lt0.01, vs.
Control.
21
RESULTS

• ?? ????(verapamil, Ver)???????????

Ver only pretreated with verapamil
VerEthanol ethanol treatment after verapamil
incubation VerRREthanol ethanol treatment
after verapamil and ruthenium red (RR, 10-5 M)
incubation VerHPEthanol ethanol treatment
after verapamil and heparin (HP, 50 mg/L)
incubation
Fig. 4. Effect of ethanol at 3 in rat aortic
rings (the rest tension was 3 g) without
endothelium precontracted with PE (10-6 M) after
verapamil (Ver, 10-6 M) pretreatment. Data are
expressed as Mean SD (n5-6). Plt0.05,
Plt0.01, vs. Ver Plt0.05, vs. VerEthanol.
22
CONCLUSION

• ????????????????????,?????????????????????????????
  ?
• ??????,???????????,3g????????????????
• ??????????????????????,????????????????????,??????
  ??????????????????
• ????????IP3???????????????????,?Ryanodine
  ????????????????

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PERSPECTIVE

• ????,?????????????????,????????,??????????????????
  ???????????????????,?????????????????????????,????
  ????????????????????????

• ??????,????????????????????????,???????????????(??
  ??????????)?????(NO?????)????????????????,????????
  ???????????????????,????????????

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ACKNOWLEDGEMENT
Acknowledgement Acknowledgement
Acknowledgement
Acknowledgement
Acknowledgement
Acknowledgement
Acknowledgement
Acknowledgement
Acknowledgement
Acknowledgement Acknowledgement
Acknowledgement

Acknowledgement
Acknowledgement Acknowledgement
Acknowledgement
Acknowledgement
Acknowledgement
Acknowledgement

• ???????????????????,???????????????,??????????,???
  ???,????????????????
• ????????????????????????????????
• ?????????????,??????????????,?????????????,???????
  ???,???????????
• ??,???????????????????????!

25
REFERENCES

• ???,??,???,???,???. ???????????????????.
  ????????, 2003, 24(24)33212234
• ???,???,???,??,??. ??????????????????????.
  ??????, 2005, 40(6)427430
• ???,???,???,???,??,??. ???????????????.
  ??????, 2003, 28( 11) 10601062
• ???,???,???,???,???,???. ???????????????????.
  ??????, 2005, 30(16) 12831286

26
REFERENCES

• ???,??,???,???,???,??. ???????????????????????.
  ??????(???),2006,35(1?)2933
• ???,??,???,??. ????????????????????.
  ??????(???),2006,35(2)178181
• ???. ??????(??)??. ???????, 2004270271
• ??,??. ????????. ?????????, 2004285288

27
REFERENCES

• CHEN Jing, GU Yong, LIN Fan, YANG Haichun, ZHU
  Weiyu, MA Ji, LIN Shanyan. Endothelin receptor
  antagonist com bined with a calcium channel
  blocker attenuates renal injury in spontaneous
  hypertensive rats with diabetes. Chinese
  Medical Journal, 2002, 115(7)972978
• Mohanty M J, Li X L. Stretch-induced Ca2 release
  via an IP3-insensitive Ca2 channel. J Am J
  Physiol Cell Physiol, 2002, 283 456462.
• McCarron J G, Bradley K N, MacMillan D, et al.
  Sarcolemma agonist-induced interactions between
  InsP3 and ryanodine receptors in Ca2
  oscillations and waves in smooth muscle. J
  Biochem Soc Tran, 2003, 31 (Pt 5) 920924.
• Bolton T B, Gordienko D V, Pucovsky V, et al.
  Calcium release events in excitation-contraction
  coupling in smooth muscle. J Novartis Found
  Symp, 2002, 246 154168.

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REFERENCES

• Rembold C M. Regulation of contraction and
  relaxation in arterial smooth muscle. J
  Hypertension, 1992, 20(2) 129137.
• LI PL, LEE HC, NELSON MT, et al. Novel Ca2
  signalling mechanisms in vascular myocytes
  symposium overview. J Acta Physiol Scand,
  2003, 179(4) 339352.
• Jaggar JH, Wellman GC, Heppner TJ, Porter VA,
  Perez GJ, Gollasch M, Kleppisch T,Rubart
  M,Stevenson AS, Lederer WJ, Knot HJ, Bonev AD,
  Nelson MT. Ca2 channels,ryanodine receptors and
  Ca(2)-activated K channels a functional unit
  for regulating arterial tone. Acta Physiol Scand,
  1998164577587.

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?????

•  ????????????,?????????,????,????????? 

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???????????????,????,???????,??????,?????????

• ??????,???,???,???????,???

????,?????????,???????
???????,??????????,??,???????????,?????????,?
?,????????????
31

• ???? 2006. 36,
• ?????????

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• Thank
• you