Fang Z, Sripairojthikoon W, Calhoun D A, Zhu S, Berecek K H, Wyss J M
Department of Cell Biology, University of Alabama at Birmingham, 35294-0019, USA.
J Hypertens. 1999 Jul;17(7):983-91. doi: 10.1097/00004872-199917070-00015.
Previous studies that were based on daytime arterial pressure recordings indicate that lifetime treatment with captopril exacerbates the hypertensive response to a high NaCl diet in spontaneously hypertensive rats (SHR) but has no such effect in normotensive Wistar-Kyoto (WKY) rats. The present study used 24-h recording methods to examine the hypothesis that during the normal waking hours of rats (night-time) the hypertensive response to a high NaCl diet is exacerbated in SHR and induced in WKY rats treated with lifetime captopril.
SHR and WKY rats were (1) untreated, (2), lifetime captopril treated or (3) lifetime captopril treated but removed from the treatment 2 weeks prior to exposure to a high (8%) NaCl diet
Compared to untreated SHR, in SHR that were continuously treated with captopril, the high NaCl diet caused a more rapid and greater rise in arterial pressure. Discontinuation of the captopril treatment did not significantly diminish this NaCl-sensitivity. In untreated WKY rats, the high NaCl diet did not alter mean arterial pressure, but in the lifetime captopril-treated WKY rats the high NaCl diet induced a rapid rise in arterial pressure. In WKY rats, discontinuation of the lifetime captopril treatment did not diminish this NaCl-induced rise in arterial pressure, even though baseline mean arterial pressure in this group is similar to that in untreated WKY rats.
Lifetime captopril treatment accelerates the hypertensive response to a high NaCl diet in SHR, and it induces a similar response in WKY rats. In both strains, the lifetime captopril treatment causes a change in the response that is not dependent on concurrent administration of the drug. This finding further suggests that lifetime captopril treatment causes a long-term resetting of cardiovascular response mechanisms.
以往基于日间动脉压记录的研究表明，卡托普利终身治疗会加剧自发性高血压大鼠（SHR）对高盐饮食的高血压反应，但对正常血压的Wistar-Kyoto（WKY）大鼠没有这种影响。本研究采用24小时记录方法来检验以下假设：在大鼠正常清醒时间（夜间），SHR对高盐饮食的高血压反应会加剧，而终身接受卡托普利治疗的WKY大鼠会出现这种反应。
将SHR和WKY大鼠分为三组：（1）未治疗组；（2）卡托普利终身治疗组；（3）卡托普利终身治疗组，但在暴露于高（8%）盐饮食前2周停药。
与未治疗的SHR相比，持续接受卡托普利治疗的SHR，高盐饮食导致动脉压升高更快、幅度更大。停用卡托普利治疗并未显著降低这种对盐的敏感性。在未治疗的WKY大鼠中，高盐饮食并未改变平均动脉压，但在卡托普利终身治疗的WKY大鼠中，高盐饮食导致动脉压迅速升高。在WKY大鼠中，停用卡托普利终身治疗并未降低盐诱导的动脉压升高，尽管该组的基线平均动脉压与未治疗的WKY大鼠相似。
卡托普利终身治疗会加速SHR对高盐饮食的高血压反应，并在WKY大鼠中诱导出类似反应。在这两种品系中，卡托普利终身治疗都会导致反应发生变化，且这种变化不依赖于药物的同时给药。这一发现进一步表明，卡托普利终身治疗会导致心血管反应机制的长期重置。
