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Vasodilation And Mechanism Of Action Of Propofol On Rat Renal Resistance Vessel

Posted on:2009-06-30Degree:MasterType:Thesis
Country:ChinaCandidate:H L ChangFull Text:PDF
GTID:2144360245469063Subject:Pharmacology
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Objective:It is suggested that the effects and mechanisms of propofol may be variant with different vascular beds.Little is known about how propofol affects renal artery.We studied the effects of propofol on responses of rat renal arteriole to some vasoactive agents.Methods:Rat isolated renal arterial tings(164.94±16.51μm) were suspended in organ chambers for isometric tension recording.The effects of propofol(10-6~10-4M) on the resting tone,KCl- and norepinephrine(NE)-induced contraction were observed.The relaxation responses to propofol alone and the combination of propofol with acetylcholine(ACh),sodium nitroprusside(SNP) or amrinone were assessed in KCl- and NE-precontracted tings.The mechanism via which propofol relaxed the artery was investigated by studying the effects of inhibition of cyclooxygenase,nitric oxide synthetase and specific K+ channels on the relaxation of propofol.Results:Propofol(up to 300μM) did not significantly affect the resting tone of rat isolated renal arteriole.Propofol(10-5,3×10-5,10-4M) depressed KCl- and NE-induced contractions. The maximal depression and IC50 were(81±8.0)%and(3.24±0.99)μM for KCl-induced contraction,and(51.0±10.0)%and>100μM for NE-induced contraction.Propofol 10-6~10-4 M relaxed both KCl- and NE-induced precontractions in concentration-dependent manner.The maximum relaxation and RC50 were 91.5±6.1%and 18.9μM for 60mM KCl-induced,and 68.7±5.2%and 70.6μM for 10μM NE-induced contractions,respectively.NE-induced contraction was more resistant to inhibition and relaxation of propofol.Indomethacin(a cyclooxygenase inhibitor) diminished the propofol-induced relaxation on both KCl- and NE-induced precontraction,while 4-aminopyridine(a voltage sensitive K+ channels(Kv) inhibitor) only reduced the relaxation in NE-induced contraction.Propofol-induced relaxation was not affected by NG-nitro-L-arginine methylester ester(a nitric oxide synthetase inhibitor), glibenclamide(a ATP-sensitive K+ channels(KATP) inhibitor).Propofol did not affect the relaxation induced by acetylcholine(an endothelium-dependent vasodilator),sodium nitroprusside(a nitric oxide releaser) or amrinone(a phosphodiesterase inhibitor). Conclusions:Propofol depresses contractions and produces remarkable relaxation on precontractions in rat isolated renal arteriole,while it does not affect the resting tone or the relaxation induced by ACh,SNP or amrinone.It is suggested that synthesis of vasodilator prostanoid and activation of Kv channel may be involved in the mechanisms via which propofol relaxes the arteriole.
Keywords/Search Tags:propofol, vasodilation, cyclo-oxygenase inhibitor, nitric oxide synthetase inhibitor, potassium channels blockers
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