Jacob Frédéric, Clark Leah A, Guzman Pilar Ariza, Osborn John W
Department of Physiology, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1519-29. doi: 10.1152/ajpheart.00206.2005. Epub 2005 Jun 3.
Centrally mediated hyperactivity of the autonomic nervous system contributes to DOCA hypertension; however, the targeted peripheral vascular bed(s) remain unclear. We propose that if renal sympathetic activity is a factor in the development of DOCA-salt hypertension, then renal denervation (RDNX) should attenuate the hypertensive response. In protocol 1, uninephrectomized RDNX (n = 9) and sham-denervated (n = 6) Sprague-Dawley rats were allowed free access to 0.9% NaCl solution and 0.1% NaCl diet. Mean arterial pressure (MAP) and heart rate were telemetrically recorded for 4 days before and 36 days after DOCA (100 mg/rat) implantation; sodium and water balances were recorded daily. Protocol 2 was similar except that saline intake in sham rats (n = 7) was matched to that observed in RDNX rats of protocol 1 for 30 days; for the last 10 days, the rats were allowed free access to saline. Before DOCA in protocol 1, MAP was lower (P < 0.05) in RDNX rats (99 +/- 1 mmHg) compared with sham rats (111 +/- 3 mmHg); however, heart rate and sodium and water balances were similar between groups. RDNX attenuated the MAP response to DOCA by approximately 50% (DeltaMAP = 22 +/- 3 mmHg, where Delta is change in MAP) when compared with sham rats (DeltaMAP = 38 +/- 6). RDNX rats consumed significantly less saline than sham rats, and cumulative sodium and water balances were reduced by 33% and 23%, respectively. In protocol 2, a similar pattern in MAP elevation was observed in RDNX and saline-restricted, sham-denervated rats even when saline restriction was removed. These results indicate that the renal sympathetic nerves are important in hypertension development but that other factors are also involved.
自主神经系统的中枢介导性多动会导致去氧皮质酮(DOCA)性高血压;然而,其靶向的外周血管床仍不清楚。我们提出,如果肾交感神经活动是DOCA-盐性高血压发生发展的一个因素,那么肾去神经支配(RDNX)应该会减弱高血压反应。在方案1中,对单侧肾切除的RDNX大鼠(n = 9)和假去神经支配大鼠(n = 6)给予自由饮用0.9%氯化钠溶液和0.1%氯化钠饮食。在植入DOCA(100 mg/只大鼠)前4天和植入后36天,通过遥测记录平均动脉压(MAP)和心率;每天记录钠和水平衡。方案2与之相似,不同的是,假手术大鼠(n = 7)的盐水摄入量与方案1中RDNX大鼠的摄入量匹配30天;在最后10天,让大鼠自由饮用盐水。在方案1中,植入DOCA前,RDNX大鼠的MAP(99±1 mmHg)低于假手术大鼠(111±3 mmHg,P < 0.05);然而,两组之间的心率以及钠和水平衡相似。与假手术大鼠(ΔMAP = 38±6)相比,RDNX使对DOCA的MAP反应减弱了约50%(ΔMAP = 22±3 mmHg,其中Δ为MAP的变化)。RDNX大鼠饮用的盐水明显少于假手术大鼠,累积钠平衡和水平衡分别减少了33%和23%。在方案2中,即使去除了盐水限制,RDNX大鼠和限制盐水摄入的假去神经支配大鼠在MAP升高方面也观察到了相似的模式。这些结果表明,肾交感神经在高血压的发生发展中很重要,但也涉及其他因素。