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Vasodilative Effect And Mechanism Of Enalapril On Thoracic Aorta Of Rats

Posted on:2009-08-09Degree:MasterType:Thesis
Country:ChinaCandidate:D WangFull Text:PDF
GTID:2144360245969063Subject:Pharmacology
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Aims: The experiment of isolated vessels was applied to investigate the vasodilative effects and the possible mechanism of enalapril on thoracic aortic rings of rats.Methods: The rats were sacrificed by anaesthesia and the thoracic aorta was quickly removed from each animal and placed in physiological salt solution (PSS). The aorta was carefully cleaned of adherent fat and connective tissue. The vessel was cut into rings of about 4mm in length. Two stainless-steel wires were passed through the lumen of each ring. One stirrup was connected to an isometric force transducer to measure tension in the vessels. The vascular tension was recorded by Powerlab multi-channel physiology signal acquisition and analysis computer system by tension transducers. The rings were placed in a 10mL organ chamber containing PSS. The rings were stretched until they exerted an optimal basal tension of 2g, and then were allowed to equilibrate for 1 hour. The solution was bubbled with 100% O2. Rings of the isolated rat thoracic aorta were mounted in organ baths and isometric contractile force was measured. Isotonic tension of thoracic aortic rings precontracted by norepinephrine (NE, 1×10-5 mol/L) or KCl (20 mmol/L) was recorded. The vasorelaxing action of enalapril and effects of various drugs which include NG-nitro-L-arginine methyl ester (L-NAME, 1×10-4 mol/L) and indomethacin (Indo, 1×10-8 mol/L) were observed in the rings.Results: (1) Enalapril (1×10-91×10-4 mol/L) had no effect on the resting tone(P>0.05). (2) Enalapril (1×10-91×10-4 mol/L) concentration-dependently reduced the contraction induced by NE (1×10-5 mol/L) or KCl (20 mmol/L). The logEC50 of enalapril respectively was -6.01±0.08 and -7.37±0.46. The Emax respectively was 37.37±1.19% and 43.86±3.56%. (3) Enalapril (1×10-91×10-4 mol/L) concentration-dependently reduced the contraction of denude-endothelium aortic rings which induced by NE (1×10-5 mol/L) or KCl (20 mmol/L). The logEC50 of enalapril respectively was -5.38±0.40 and -6.78±0.29. The Emax respectively was 30.38±1.51%and 26.38±1.49%. There was significant difference between the rings with intact and denuded endothelium (P <0.05). (4) Enalapril (1×10-91×10-4 mol/L) attenuated the contraction induced by NE (1×10-5 mol/L) with and without NG-nitro-L-arginine methyl ester (L-NAME, 1×10-4 mol/L). The logEC50 of L-NAME group was -6.02±0.41 and the Emax was 22.36±2.74%. There was significant difference between L-NAME group and enalapril single group (P <0.05). (5) Enalapril (1×10-91×10-4 mol/L) attenuated the contraction induced by NE (1×10-5 mol/L) with and without pretreated by indomethacin (1×10-8 mol/L). The logEC50 of indomethacin group was -6.00±0.22 and the Emax was 23.81±2.74%. There was significant difference between indomethacin group and enalapril single group (P <0.05). (6) Enalapril (1×10-91×10-4 mol/L) attenuated the contraction induced by KCl (20 mmol/L) with and without pretreated by NG-nitro-L-arginine methyl ester (L-NAME, 1×10-4 mol/L). The logEC50 of L-NAME group was -7.60±0.29 and the Emax was 9.69±0.61%. There was significant difference between L-NAME group and enalapril single group (P<0.05). (7) Enalapril (1×10-91×10-4 mol/L) attenuated the contraction induced by KCl (20 mmol/L) with and without pretreated by indomethacin (1×10-8 mol/L). The logEC50 of indomethacin group was -6.64±0.30 and the Emax was 32.01±3.49%. There was significant difference between indomethacin group and enalapril single group (P <0.05).Conclusions: (1) Enalapril had no effect on the resting tone. (2) Enalapril preferentially antagonized contraction induced by NE (1×10-5 mol/L) or KCl (20 mmol/L) in concentration-dependent manner. (3) Enalapril preferentially antagonized the contraction of rat thoracic artery in a endothelium-dependent manner. The vasorelaxation of enalapril was relevant to the production of NO and prostacyclin.
Keywords/Search Tags:enalapril, thoracic aorta, vasodilation, endothelium, nitric oxide, prostacyclin
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