Paraoxon attenuates vascular smooth muscle contraction through inhibiting Ca2+ influx in the rabbit thoracic aorta.
We investigated the effect of paraoxon on vascular contractility using organ baths in thoracic aortic rings of rabbits and examined the effect of paraoxon on calcium homeostasis using a whole-cell patch-clamp technique in isolated aortic smooth muscle cells of rabbits. The findings show that administration of paraoxon (30 microM) attenuated thoracic aorta contraction induced by phenylephrine (1 microM) and/or a high K+ environment (80 mM) in both the presence and absence of thoracic aortic endothelium. This inhibitory effect of paraoxon on vasoconstrictor-induced contraction was abolished in the absence of extracellular Ca2+, or in the presence of the Ca2+ channel inhibitor, verapamil. But atropine had little effect on the inhibitory effect of paraoxon on phenylephrine-induced contraction. Paraoxon also attenuated vascular smooth muscle contraction induced by the cumulative addition of CaCl2 and attenuated an increase of intracellular Ca2+ concentration induced by K+ in vascular smooth muscle cells. Moreover, paraoxon (30 microM) inhibited significantly L-type calcium current in isolated aortic smooth muscle cells of rabbits. In conclusion, our results demonstrate that paraoxon attenuates vasoconstrictor-induced contraction through inhibiting Ca2+ influx in the rabbits thoracic aorta.
Zhou
Shouhong
S
Department of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha, Hunan 410078, China.
Liu
Liying
L
Yang
Xuhong
X
Wu
Shujin
S
Chen
Gengrong
G
D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010261:Paraoxon / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D011189:Potassium Chloride; D014700:Verapamil; D010261:Paraoxon; D002118:Calcium
J Toxicol Environ Health A. 2007 Sep;70(18):1556-67
17710615
Am J Physiol Cell Physiol. 2005 Apr;288(4):C769-83
15761211
Brain Res. 2006 Apr 14;1083(1):110-7
16566905
Eur J Pharmacol. 2007 Oct 1;571(2-3):81-7
17599827
Arch Oral Biol. 2000 Aug;45(8):621-38
10869474
Pharmacol Toxicol. 1990 Jul;67(1):27-35
2395813
Am J Physiol Regul Integr Comp Physiol. 2002 Jul;283(1):R29-45
12069928
Toxicol Lett. 2001 Mar 31;120(1-3):343-51
11323193
J Cardiovasc Pharmacol. 2005 Jun;45(6):586-90
15900233
Pharmacol Ther. 2005 Sep;107(3):286-313
16005073
J Appl Physiol (1985). 2004 Sep;97(3):1091-7
15333628
J Toxicol Environ Health. 1995 Feb;44(2):167-87
7853421
Rev Physiol Biochem Pharmacol. 2003;150:91-139
12884052
J Cardiovasc Pharmacol. 2009 Apr;53(4):277-89
19390346
J Biomed Biotechnol. 2002;2(3):117-119
12488574
Neurotoxicology. 1997;18(1):283-97
9216006
Toxicol Lett. 1998 Dec 28;102-103:509-13
10022304
Acta Pharmacol Sin. 2007 Nov;28(11):1797-802
17959031
Am J Physiol Lung Cell Mol Physiol. 2007 Apr;292(4):L915-23
17158603
Toxicology. 1994 May 31;90(1-2):81-91
8023345
J Pharmacol Exp Ther. 1996 Sep;278(3):1175-87
8819500
Mol Pharmacol. 2000 Sep;58(3):577-83
10953051
Am J Physiol Renal Physiol. 2005 Jul;289(1):F137-44
15713909
Hum Exp Toxicol. 1997 Oct;16(10):563-9
9363473
J Cardiovasc Pharmacol. 2007 Aug;50(2):155-61
17703131
Toxicol Appl Pharmacol. 1997 Oct;146(2):227-36
9344890
Toxicology. 1998 Jan 16;125(1):13-9
9585096
J Appl Toxicol. 2007 Nov-Dec;27(6):582-8
17370251
Invert Neurosci. 2005 Nov;5(3-4):119-33
16172884
J Cardiovasc Pharmacol. 2008 Oct;52(4):293-9
18791467
Am J Physiol Heart Circ Physiol. 2008 Jun;294(6):H2421-7
18441199
Physiol Rev. 1996 Oct;76(4):967-1003
8874491
J Toxicol Environ Health. 1996 Jul;48(4):397-411
8691509
Eur J Pharmacol. 2000 Sep 22;404(3):353-9
10996600
Am J Physiol. 1995 Apr;268(4 Pt 1):C799-822
7733230
Brain Res. 1991 Nov 1;563(1-2):303-5
1664774
Int Arch Occup Environ Health. 2009 Jul;82(7):833-42
19424713
J Biomed Biotechnol. 2006;2006(2):97803
16883058