Study Of Effects And Mechanisms Of Renal Nerves On Renal Hypertension

Objective:To establish the model of renal hypertension in rats; to compare the dynamic changes in blood pressure, electrical activity of paraventricular nucleus(PVN) of renal hypertension, the Ang II in blood and expression of Ang II in PVN between rats with of without renal nerve, thus to explore the relation between the electrical activity of PVN and renal hypertension, and to find out the role of renal nerve on the process of renal hypertension and its mechanism. Methods:(1) To establish the model of renal hypertension:left renal artery was ligated with acupuncture needle of different diameter(0.10mm,0.15mm,0.20mm,0.25mm and0.30mm), then extracted needle and made left renal artery stenosis. Monitoring blood pressure after operations continuously, the standard of successful model is that the diastolic pressure kept higher than100mmHg.(2) To explore the role renal nerve on renal hypertension: forty-five SD rats (130±30g) were randomly divided into three groups:①Removal renal nerve group:separating and constricting left renal artery, and separating and shearing left renal nerve. The blood pressure of rats’ tales was measured and observed with non-invasive tail cuff method. After the models were stable, the electrical activity of PVN was recorded with metal microelectrode, and blood Ang II and the expression of Ang II receptor in PVN was detected.②Renal nerve group:separating and constricting left renal artery, remaining left renal nerve. The other treatments were same with removal renal nerve group.③Sham operation group:separating left renal artery and left renal nerve, to imitate the operation of constricting left renal artery and shearing left renal nerve. The other treatments were same with groups above.(3) Statistics analysis All experimental datum were expressed as the mean value±standard difference(x±s), the mean values comparision used one-way ANOVA, repeated measures and paired t-test. The difference was considered significance when the p value was less than0.05. Results:(1) The establishment of renal hypertension model:1-2weeks after left renal arteriostenosis operation, the blood pressure with each diameters of needles increased, especially in the second week. There was significant difference compared with control group (P<0.05), and no significant difference between groups. The blood pressure of0.1mm group remained high level in the third week, and fell back to normal level in the forth week. The kidneys were badly swelling, and no structure existed in renal parenchyma, showing caseous necrosis. The blood pressure of0.20mm group decreased gradually after three weeks, but most animal’s kidneys were shown atrophy and calcification. The blood pressure of0.25mm group remained at high levels, five weeks reached the highest,153.68±24.05/120.03±18.98mmHg. The renal envelope was intact, and no atrophy, calcification and swelling existed. The blood pressure of0.30mm and0.35mm groups all recovered to normal level three weeks later, and no significant changes found in the kidneys. Therefore, needles with0.25mm diameter could duplicate the renal hypertension model successfully.(2) Effects of renal nerve on blood pressure of renal hypertension:One week after surgery, the blood pressure of each group all rose, among the total, the renal nerve group heightened obviously, and there was a significant difference between renal nerve group and other two groups; Two weeks after surgery, the blood pressure of sham operation group descended continuously, and didn’t recover until the third week; The blood pressure of rats with or without renal nerve heightened progressively; Compared with sham operation group, there was a significant difference on systolic pressure, diastolic pressure and mean arterial pressure at each observation point. Of the total, the blood pressure heightened greater in renal nerve group, and there was a significant difference between renal nerve group and removal renal nerve group on systolic pressure, diastolic pressure and mean arterial pressure in the third or fourth week.(3) Effects of renal nerve on the electrical activity of renal hypertension:There was no significant difference between sham operation group and animals of control state in electrical activity of PVN. Compared with sham operation group, the discharge time prolonged, the amplitude, frequency, period and integral of bioelectricity increased apparently in renal nerve group(P<0.05). Compared with removal nerve group, the discharge time of renal group prolonged, the amplitude, frequency, period and integral of bioelectricity increased greatly(P<0.05). (4) plasma renin, aldosterone levels, sham operation group showed the highest, followed by retention group, the lowest is to remove the group (P<0.05) the difference was statistically significant (P<0.05); and the sham operation group, retaining group, removal of group three group of aldosterone content difference does not have statistical significance (P>0.05).(5) the hypothalamic paraventricular nucleus Ang II receptor expression, sham operation group morphological differences, and sham operation group, retaining group, removal group and a three group of paraventricular nucleus Ang II receptor expression difference does not have statistical significance (P>0.05). Conclusion:The certain renal arteriostenosis can generate persistent renal hypertension; Renal nerve plays a role in the process of renal hypertension, and to remove renal nerve may lower the blood pressure level of renal hypertension; The electrical activity has strengthen during renal hypertension, so renal nerve has contributed to adjust the electrical tonicity of PVN, in contrast, the electrical activity has lowered after renal nerve was removed; Renal nerve acts as afferent nerve to excite PVN, so humoral and neuron elements both anticipate the occurrence and development of renal hypertension.