| ObjectiveThis study was designed to observation of betaine and enalapril alone and in combina-tion with antihypertensive effect on renal hypertensive rats and protective effects on targetorgans, application prospects and to explore its mechanism and betaine in the treatment ofhypertension.MethodsRenal hypertensive rats were randomly divided into8groups,10rats in each group, r-espectively, model group, low, middle, high dose betaine group (50,100,200mg/kg), ena-lapril group (3mg/kg), enalapril (3mg/kg) and betaine in low, midle,high dose(50,100,200mg/kg) group; the same batch of10Wistar rats in the sham operation group. Every day,rats in each group were intragastric administration for1times, continuous administration f-or8Weeks, model group and sham operation group was given equal volume of physicalo-gical saline.Administration the drug fourth and8weeks, non-invasive tail cuff systolic blood pre-ssure were measured in rats. At the end of the eighth week dosing day, chloral hydrate an-esthesia, the plasma, heart, kidney. Cardiac left ventricular part, immediate weighing, calc-ulation of total ventricular weight index (VMI), the left ventricular weight index (LVMI),right ventricular weight index (RVMI), left ventricular wall thickness (LVWT), right vent-ricular wall thickeness (RVWT), interventricular septum (IVST).The left ventricle, kidneycut into two parts, the upper part of theapical, kidney paraffin section, HE staining, the restas homogenate. Determination of plasma homocysteine (Hcy) levels; active oxygen plas-ma, heart, kidney tissue homogenate were measured in the cluster (ROS), malondialdehyde(MDA), nitric oxide (NO), angiotensinII (Ang II), endothelin (ET) content and superoxidedismutase (SOD), nitric oxide synthase (NOS), glutathione peroxidase (GSH-Px), renin activity (Renin).Results1. The affective of betaine and enalapril alone and in combination with hyperte-nsion model rats: in experiment period always maintain the stability of the effects onblood pressure. Enalapril alone and in combination with different doses of betaine group r-ats blood pressure decreased significantly (P<0.01), enalapril alone and combined with hy-potension group had no significant difference, the dose betaine alone had no significant ef-fect on blood pressure (P>0.05). Show that betaine without antihypertensive effect on ratswith renal hypertension, antihypertensive effect of enalapril also no obvious influence.2. The protective effect of betaine and enalapril alone and in combination withon target organs:compared with the model group, betaine or enalapril alone and with thecombination of the two drugs could reverse hypertension induced left ventricular remo-deling, VMI, LVMI and LVWT were significantly decreased in all groups (P<0.01); andtwo kinds of drugs with the single group comparison, has obvious synergistic effect on im-proving left ventricular remodeling with a combination of the two drugs (P<0.05), the highdose betaine and enalapril combined with various cardiac parameters were consistent withthe control group. HE staining showed that, single, enalapril and two drug group and mod-el group compared with betaine, pathologic model group target organ is obviously improv-ed, protective effect.3. The affective of betaine and enalapril alone or in combination with on the Hcy:the results of the experimen showed that the betaine alone or in combination with enalaprilcan decrease the content of Hcy in plasma of renal hypertension rats (P<0.05, P<0.01), en-alapril alone had no obvious effects of decreasing (P>0.05), and the two drugs combinedwith the better (P<0.01).4. The effect of betaine and enalapril alone or in combination with on antioxida-ntion: the experiment results showed that, the single use of betaine or enalapril or the twodrugs combined with all have antioxidant activity, can reduce the renal hypertensive ratplasma, myocardium, kidney tissue in ROS, content of MDA, increase the activity of SOD,GSH-Px (P<0.05, P<0.01); synergistic with a combination of the two drugs (P<0.01).5. The affective of betaine or enalapril alone and in combination with results onNO, ET-1contents: the experiment results showed that, renal hypertensive rats in the mo-del group, the content of ET-1in plasma of myocardial, kidney tissue was significantly in-creased, NO content decreased significantly, the plasma ET-1content of myocardial, kidn-ey tissues in the betaine, enalapril and two drugs combined with were significantly reduced, the content of NO were significantly increased (P<0.05, P<0.01), have a synergistic effectwith a combination of the two drugs (P<0.01).6. The effects of betaine and enalapril alone or in combination with on AngII co-ntent and Renin activity: the betaine, enalapril and two drugs combination can decreasethe activation of the RAS system, to decrease the level of Renin AngII content in rats withrenal hypertension, myocardial in kidney tissue of (P<0.05, P<0.01), two the medicinecombination has obvious reduction (P<0.01)Conclusion1. Enalapril alone or combined with betaine has obvious antihypertensive effect on re-nal hypertensive rats; Betaine alone had no significant antihypertensive effect, there is noobvious influence its antihypertensive effect on enalapril.2. Betaine, enalapril or two drug combination has a protective effect on target organsof renal hypertensive rats, can deteriorate left ventricle, aortic remodeling reversal causedby hypertension, alleviate renal damage; the two drugs combined with the target organprotection has a synergistic effect.3. Betaine alone and in combination with enalapril can decrease the content of Hcy inplasma of renal hypertension rats, enalapril alone had no obvious effects of decreasing, sh-ow that betaine can reduce the injury effects of Hcy in renal hypertensive rats improvedtarget organ, and the two drugs combined with the effect of better.4. Betaine, enalapril or two druas combined can decreased significantly myocardial,kidney tissue in ROS, MDA content, increase SOD, GSH-Px activity in renal hype-rtension rats, indicated that the protective effect of betaine on target organ damage is likelyto play a role in the improvement of oxidative stress level in the body, have a synergistic e-ffect with the combination of the two drugs.5. The content of ET-1in plasma of myocardial, kidney tissue was significantlyincreased, NO content decreased significantly in the model group rats, the myocardial, ki-dney tissue of plasma ET-1content were significantly decreased in the betaine, enalapril ortwo drugs combined, NO content increased obviously, indicated that betaine can improveendothelial function of rat kidney hypertension, have a synergistic effect with a combinati-on of the two drugs.6. Betaine, enalapril alone or two drugs combined can decrease the level of Renin andAngII in the renal hypertension rats, by adjusting the RAS system to protect the targetorgan damage. |
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