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Effects Of Enalapril And Losartan On Plasma Homocysteine, Nitric Oxide And Renal CAMP, CGMP In Spontaneously Hypertensive Rats

Posted on:2004-09-11Degree:MasterType:Thesis
Country:ChinaCandidate:Y X HuFull Text:PDF
GTID:2144360092486361Subject:Elderly cardiovascular disease
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Homocysteine (Hey) is an independent risk factor of myocardial infarction, stroke, and atherosclerosis. However, the relationship between Hey and hypertension is equivocal. The abnormal metablism of renal might play an important role in the progress of hypertension. Therefore, the levels of cAMP and cGMP, as mediator for angiotensin II (Angll) and nitric oxide (NO), respectively, would be changed during hypertension. Enalapril and Losartan not only have good effect in treating hypertension but also have protection on vascular and renal , the benefits may be accomplished by improving those abnormal changes .Objective : Probed into the relationship between plasma Hey, folate, Vitamin B|2 (VitB|2), renal cAMP, cGMP levels and hypertension. Evaluated effects of Enalapri and Losartan on those changes in Spontaneously Hypertensive Rats(SHR).Materials and Methods Eighteen 14-week-old male SHR were randomly allocated to three groups (n=6) and were treated with enalapril (ISmg-kg^-d"1) or losarta^SV-Smg-kg''^"1), equal volume of distilled water were administered respectively for 2 weeks by gavage. At the end of the 2 weeks treatment, the levels of renal cAMP, cGMP and Angll were quantified by radioimmunossay, plasma and renal nitrate (NO3~) from metabolic production of NO were measured by Griess reaction. Fluorescencepolarization immunoassay was used to measure plasma homocysteine level, an ion capture assay was used for the quantitative determination of folate, and microparticle enzyme intrinsic factor assay was used for the quantitative determination of VitB)2.Results: 1. There were no differences of plasma Hey and folate between subgroups of SHR and WKY. Levels of VitB,2 were 1397.8 ?103.72 pg/ml and 1167.5 ?113.99 pg/ml in SHR and WKY, respectively; significantly higher in SHR than in WKY (P<0.05)\ 2. No correlation between blood pressure and Hey concentration was found in rats without anti-hypertensive medication ( r= - 0.1 \,p=0.718). The level of plasma Hey in WKY and SHR group was negatively related with that of VitBi2 ( r= -0.8031, P<0.05) ; 3. Both administration of Enalapril and Losartan can significantly reduced blood pressure (from 180.6 ?17.4 mmHg to 126.5 ?8.6 mmHg, 174.2 ?9.3 mmHg to 123.2 ?11.1 mmHg, respectively, P<0.01), but had no effect on Hey, folate and elevated VitB)2 levels; 4. Levels of plasma NO3~ were 32.75?.09umol/L and 41.03?.75umol/L in SHR and WKY, respectively; significantly lower in SHR than in WKY ( P<0.05 ). Enalapril elevated plasma NO3" concentration (41.23?.93u,mol/L) compared with that in SHR ( P<0.05 ). Losartan treatment had tendency of elevating the level of plasma N(V ( 35.06?.17umol/L ) , but there was no statistic significance between Losartan group and SHR group ( P>0.05); 5. Level of renal Angll was significantly increased in SHR group ( 36.92?.38 pmol/g) compared with that in WKY (21.53?.37 pmol/g, P<0.01\ In comparision with SHR group , renal Angll was decreased by Enalapril (26.47?.47 pmol/g, P<0.01\ increased by Losartan (42.69?2.88 pmol/g, P<0.05); 6. The levelof renal cAMP was lower in SHR (881.71?9.91 pmol/g) than in WKY ( 1169.66?6.91 pmol/g, P<0.01 ) , and can be elevated with Enalapril (1220.30?3.49 pmol/g, P<0.07); 7. NO3' of renal in SHR control group(20.43?.16umol/L) was significantly reduced compared with that in WKY group (25.98?.94umol/L, P<0.01). NO3"concentrations in Enalapril and Lorsartan group were 26.37?.96umol/L and 25.78?.08umol/L, respectively; both higher than in SHR group (P<0.05)\ 8. Concentration of renal cGMP in SHR control group was reduced significantly compared with that in WKY group (193.54?4.80pmol/g vs 228.49?3.04pmol/g, P<0.01)\ renal cGMP in Enalapril and Lorsartan group were 222.93?.22 pmol/g and 215.78?.36 pmol/g, respectively, increased significantly compared with that in SHR group ( P<0.01, P<0.05 ) . The level of renal cGMP was positively related with NO3" in SHR group (r=0.8689, P<0.01).Conclusion: 1. There was no differences of plasma Hey and folate between of SHR and WKY. No...
Keywords/Search Tags:Hypertension, Enalapril, Lorsartan, Homocysteine, nitric oxide, cAMP, cGMP, angiotensin II
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