Cipolla Marilyn J, Smith Jeremiah, Bishop Nicole, Bullinger Lisa V, Godfrey Julie A
Department of Neurology, University of Vermont, 89 Beaumont Ave, Given C454, Burlington, VT 05405, USA.
Hypertension. 2008 Apr;51(4):1052-7. doi: 10.1161/HYPERTENSIONAHA.107.100545. Epub 2008 Feb 7.
Previous studies have shown that pregnancy prevents hypertensive remodeling of cerebral arteries. In the present study, we sought to determine whether pregnancy could reverse preexisting remodeling. Nonpregnant virgin Sprague-Dawley rats were treated with the NO synthase inhibitor nitro-l-arginine (0.5 g/L in drinking water) for 2 weeks before mating, after which treatment continued until late gestation for a total of 5 weeks. Pregnant animals with preexisting hypertension (n=6) were compared with nonpregnant animals that were treated with nitro-l-arginine for either 2 (n=8) or 5 (n=9) weeks and compared with nontreated controls (n=8). Blood pressure, passive and active diameters, wall thickness, media thickness, and passive distensibility of cerebral arteries were compared between groups. Treatment with nitro-l-arginine caused a significant increase in mean arterial pressure in all of the groups compared with controls that was sustained for the entire study: 103+/-3 versus 137+/-2, 141+/-4, and 140+/-7 mm Hg (P<0.01). Both 2 and 5 weeks of hypertension caused inward eutrophic remodeling in nonpregnant animals, characterized by decreased inner and outer lumen diameters and no change in media thickness. Pregnancy reversed this remodeling, because late-pregnant animals with preexisting hypertension had inner and outer diameters similar to controls. Passive distensibility was significantly less, and active myogenic tone increased in all of the hypertensive animals, independent of pregnancy. These results demonstrate that pregnancy reverses preexisting hypertensive remodeling of cerebral arteries without a decrease in blood pressure. This reversal of protective remodeling during hypertension in pregnancy may be detrimental by lowering the upper limit of autoregulation, whereas blood pressure remains elevated.
先前的研究表明,妊娠可预防脑动脉的高血压重塑。在本研究中,我们试图确定妊娠是否能逆转已存在的重塑。未孕的处女Sprague-Dawley大鼠在交配前2周用一氧化氮合酶抑制剂硝基-L-精氨酸(饮用水中浓度为0.5 g/L)处理,之后该处理持续至妊娠晚期,共5周。将患有已存在高血压的妊娠动物(n = 6)与用硝基-L-精氨酸处理2周(n = 8)或5周(n = 9)的未孕动物进行比较,并与未处理的对照组(n = 8)进行比较。比较各组之间的血压、被动和主动直径、壁厚度、中膜厚度以及脑动脉的被动扩张性。与对照组相比,硝基-L-精氨酸处理使所有组的平均动脉压显著升高,且在整个研究过程中持续存在:103±3与137±2、141±4和140±7 mmHg(P<0.01)。2周和5周的高血压均导致未孕动物出现内向性营养性重塑,其特征为内外腔直径减小且中膜厚度无变化。妊娠逆转了这种重塑,因为患有已存在高血压的妊娠晚期动物的内外直径与对照组相似。所有高血压动物的被动扩张性均显著降低,且主动肌源性张力增加,与妊娠无关。这些结果表明,妊娠可逆转已存在的脑动脉高血压重塑,而血压并未降低。妊娠期间高血压时这种保护性重塑的逆转可能通过降低自动调节的上限而有害,而血压仍保持升高。