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Renal Sympathetic Denervation For Resistant Hypertension In Spontaneously Hypertensive Rats

Posted on:2013-07-08Degree:MasterType:Thesis
Country:ChinaCandidate:J LiuFull Text:PDF
GTID:2234330374478582Subject:Internal Medicine
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1. Background and Objective:Renal innervation is the main sympathetic postganglionic fibers fo rmed a densenetwork covering the blood vessels and nephron of the kidney, which dominated theactivities of the kidney. Renal sympathetic nerve activity (RSNA) plays an important role inregulating body sodium metabolism and renal endocrine function. Activation of renalsympathetic nerve to promote sodium reabsorption, norepinephrine (NE) and reninsecretion and release, renal vasoconstriction, renal blood flow (RBF) reduced,all of whichmediated increasing of blood pressure.Long-term regulation of blood pressure is mainly accomplished by the kidneys. RSNAhas already been enhanced in the early stage of the patients with hypertension, which cancause the continuing rising of blood pressure by increasing the NE spillover rate. Studieshave shown that in the prehypertension, the RSNA had been enhanced. Thus provide avaluable theoretical basis for the treatment of hypertension to the renal denervation surgery.Firstly in our study, through the implementation of different blood pressure levels inthe renal denervation surgery, we investigated the effect of the renal denervation on bloodpressure in hypertensive and normotensive rats and explore the mechanisms behind;Secondly, through the implementation of different ages in the renal denervation surgery, westudied the therapeutic effect of different ages of hypertension body and therapeutic value.2. Methods:12-week-old rats were divided into hypertension group (SHR) and normotens ive group(WKY). In addition, SHRs were divided into the12-week-old of youth group and 30-week-old of middle-aged group, each age group was divided into the renal denervationgroup (RDX) and sham operation group (Sham); Our observation time point was2daysbefore denervation, after denervation on2d,4d,7d,14d,30d.2.1Blood pressure was measured while awake and quiet. The rats were put in themetabolic cages to measure the calculation of water and sodium’s intake and excretion inthe24hours with constant temperature (21±2℃), humidity (50±5%) with a12:12hourlight/dark cycle;2.2The rats should be fasted with water available ad libitum one night beforedenervation, then the renal nerve surgery and sham operation were be implementedrespectively.2.3Blood pressure was measured once a day at10a.m. by the rat tall-cuff bloodpressure meter (BP-98A, Softron, Japan). In addition, we detected the intake and excretionof sodium and water.2.4On the2d,4d,7d,14d,30d after surgery, the corresponding group of rats weresacrificed, plasma, renal tissue content of NE and renin activity were be detected by Elisa;The expression of α1and β1-adrenergic receptor on mRNA levels were determined byRT-PCR and these expression on protein levels were determined by Western Blotting.3. Results:3.1There was no denervative effect when10%phenol rubbed the surface of the renalartery. If we wrapped renal artery with cotton cloth infiltrated of phenol can reach the effectof the denervation.3.2Renal denervation could quickly and effectively lower blood pressure in12-week-old SHR, with no effect of blood pressure in the normotensive WKY rats;3.3Regardless of the SHR group and WKY group, there was no significant effects tothe renal nerves on sodium and water metabolism;3.4There was a sustained lower blood pressure levels of12-week-old SHR. However,with the denervation of the30-week-old SHR there was just a transient effect ofanti-hypertension, blood pressure began to increase gradually to the preoperative level afterone week.3.5Blood pressure lower was accompanied by NE spillove r and renin activityattenuation. 4. Conclusion:4.1Renal nerves play a more important role in maintaining the blood pressure but it isnot the essential factor;4.2Renal denervation does not affect the renal function without the change of sodiumand water metabolism;4.3Drop in blood pressure has relation to the reduce of the NE secretion and theinhibition of RAAS;4.4The expression of the α1, β1-adrenergic receptor was up-regulated with theattenuation of blood pressure;4.5Renal denervation should not be the first choice if the changes existing in renalstructure and function.
Keywords/Search Tags:spontaneously hypertensive rats, renal denervation, sympathetic nerve, blood pressure
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