Rodriguez-Porcel M, Krier J D, Lerman A, Sheedy P F, Romero J C, Napoli C, Lerman L O
Department of Internal Medicine, Division of Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
Hypertension. 2001 Feb;37(2 Pt 2):774-80. doi: 10.1161/01.hyp.37.2.774.
Hypercholesterolemia and hypertension are both risk factors for end-stage renal disease. This study was designed to examine whether their coexistence augmented impairment in renal function and redox status. Regional renal hemodynamics and function in response to vasoactive challenges with acetylcholine or sodium nitroprusside were quantified by using electron-beam computed tomography in pigs after 12 weeks of either a normal (n=10) or hypercholesterolemic (n=10) diet, renovascular hypertension (n=7), or combined hypercholesterolemia+hypertension (n=6). The hypercholesterolemic and hypercholesterolemic+hypertensive groups had significantly increased serum cholesterol levels, whereas in the hypertensive and hypercholesterolemic+hypertensive groups, mean arterial pressure was significantly elevated compared with the group fed a normal diet. Basal regional renal perfusion and glomerular filtration rates were similar among the groups. In response to acetylcholine, cortical perfusion increased in normal animals (15.6+/-4.7%, P=0.002) but not in hypercholesterolemic or hypertensive animals (8.0+/-7.4% and 8.2+/-5.9%, respectively; P>0.05). Moreover, in the hypercholesterolemic+hypertensive group, cortical perfusion response was further attenuated (2.5+/-4.8%, P=0.02) and significantly different from the group fed a normal diet (P<0.05). The response to sodium nitroprusside followed a similar pattern, and the impairment was augmented in the hypercholesterolemic+hypertensive group. The functional abnormalities in hypercholesterolemia or hypertension were associated with a decrease in systemic and/or renal tissue levels of oxygen radical scavengers that was again accentuated in hypercholesterolemia+hypertension. These results demonstrate that concurrent hypercholesterolemia and hypertension have a greater detrimental effect on renal perfusion responses compared with hypercholesterolemia or hypertension alone, associated with a marked pro-oxidant shift in redox status. These effects may potentially augment renal functional impairment and play a role in the initiation and progression of renal injury in hypertension and atherosclerosis.
高胆固醇血症和高血压都是终末期肾病的危险因素。本研究旨在探讨它们同时存在是否会加重肾功能损害和氧化还原状态异常。在猪分别接受12周正常饮食（n = 10）、高胆固醇饮食（n = 10）、肾血管性高血压（n = 7）或高胆固醇血症合并高血压（n = 6）后，使用电子束计算机断层扫描对乙酰胆碱或硝普钠血管活性刺激后的局部肾血流动力学和功能进行定量分析。高胆固醇血症组和高胆固醇血症合并高血压组的血清胆固醇水平显著升高，而高血压组和高胆固醇血症合并高血压组的平均动脉压与正常饮食组相比显著升高。各组间基础局部肾灌注和肾小球滤过率相似。对乙酰胆碱的反应，正常动物皮质灌注增加（15.6±4.7%，P = 0.002），但高胆固醇血症或高血压动物未增加（分别为8.0±7.4%和8.2±5.9%；P>0.05）。此外，在高胆固醇血症合并高血压组，皮质灌注反应进一步减弱（2.5±4.8%，P = 0.02），且与正常饮食组有显著差异（P<0.05）。对硝普钠的反应遵循类似模式，高胆固醇血症合并高血压组的损害加重。高胆固醇血症或高血压时的功能异常与全身和/或肾组织中氧自由基清除剂水平降低有关，在高胆固醇血症合并高血压时这种降低再次加剧。这些结果表明，与单独的高胆固醇血症或高血压相比，同时存在的高胆固醇血症和高血压对肾灌注反应有更大的有害影响，伴有氧化还原状态明显的促氧化转变。这些作用可能会加重肾功能损害，并在高血压和动脉粥样硬化性肾损伤的发生和发展中起作用。
