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Effect And Mechanisms Of Midazolam On Contractions Of Porcine Coronary Artery

Posted on:2011-09-03Degree:MasterType:Thesis
Country:ChinaCandidate:J J RenFull Text:PDF
GTID:2154360305478838Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Objective To investigate the effects and the possible mechanism of midazolam on porcine isolated coronary artery rings pre-contracted by potassium chloride(KCl).Methods The instrument of isolated artery rings was used. The response action of midazolam and effect of various drugs were observed in the rings.Results (1) Midazolam(3×10-6~1×10-4mol/L)had no effect on the resting tone (P>0.05). (2) Midazolam(3×10-6~1×10-4mol/L) respectively concentration-dependently reduced the contrac-tion induced by KCl. There was significant difference compared with control group (P<0.01). (3) Midazolam(3×10-6~1×10-4 mol/L) respectively concentration-dependently reduced the contraction of denude-endothlium porcine coronary artery rings which induced by KCl. There was significant difference between the rings with intact and denude endothelium (P<0.01). (4) On KCl-induced precontraction,midazolam's relaxation was depressed by L-NAME(P<0.01),the blend of L-NAME and L-Arg(P<0.05),but was not affected by L-Arg(P>0.05) or 1400W(P>0.05).(5) The contraction was not prevented by pretreatment with the NCX inhibitors KB-R7943(1×10-6mol/L)(P>0.05).(6)On KCl-induced precontraction,3×10-6~1×10-4mol/L midazolam's vasodilation can be inhibited by Gli(P<0.01). (7) On KCl-induced precontraction, TEA(P>0.05), BaCl2(P>0.05)and 4-AP(P>0.05) can't inhibit midazolam's vasorelaxant effects.Conclusion (1)Midazolam didn't affect the resting tone of porcine isolated coronary artery rings. (2) Midazolam could produce remarkable vasodilatation on KCl pre-contracted porcine isolated coronary artery rings. Its relaxtion effect is via endothelium-dependent mechanisms and relevant to the production of NO, The exogenous NO, iNOS and PGI2 participate midazolam's relaxtion effect. (3)Na+/Ca2+ exchanger is not involved midazolam's vasodilatation on KCl pre-contracted porcine coronary artery rings. (4)The relaxant mechanism of midazolam may be concerned with KATP channel. The Kir channel,BKCa channel and Kv channel may be not involved.
Keywords/Search Tags:midazolam, porcine coronary artery rings, vascular tone, NO, potassium channel, potassium channel inhibitor
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