Danchuk S, Sukhanov S, Horvat D, Uddin M N, Puschett J B
Section of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Am J Nephrol. 2008;28(1):8-13. doi: 10.1159/000108756. Epub 2007 Sep 20.
BACKGROUND/AIMS: There are two major pathophysiologic processes involved in the development of hypertension: (1) expanded extracellular fluid volume and (2) vasoconstriction. We have developed a model of preeclampsia in the rat, in which excessive volume expansion (VE) plays a role. These animals excrete increased amounts of the bufodienolide, marinobufagenin (MBG), even before their hypertension and proteinuria become established. Furthermore, their hypertension is corrected by administration of resibufogenin (RBG), a compound structurally similar to MBG.
We studied two models of experimental hypertension in the nonpregnant animal, produced either by deoxycorticosterone acetate (DOCA)-salt administration or by angiotensin infusion.
RBG administered to the DOCA-salt rats lowered blood pressure and reduced proteinuria in the VE animals, but had no affect on the rats infused with angiotensin. Furthermore, although the production of superoxide anion in the aortas of both groups of hypertensive rats was increased over control, RBG reduced these levels to normal in the VE (DOCA-salt) animals only. RBG had no effect in the angiotensin-infused rats. The urinary excretion of angiotensinogen did not rise in VE-mediated hypertension, but did increase in the angiotensin-infused rats.
MBG plays an important role in the causation of hypertension in the VE rats, but not in the vasoconstrictive model. RBG is effective only in VE-mediated hypertension.
背景/目的：高血压的发生涉及两个主要的病理生理过程：（1）细胞外液量增加和（2）血管收缩。我们已经建立了一种大鼠子痫前期模型，其中过度的容量扩张（VE）起作用。这些动物甚至在高血压和蛋白尿形成之前就排泄出增加量的蟾毒配基、海蟾蜍精（MBG）。此外，给予结构与MBG相似的化合物瑞香毒素（RBG）可纠正它们的高血压。
我们研究了非妊娠动物实验性高血压的两种模型，一种由醋酸脱氧皮质酮（DOCA）-盐给药产生，另一种由输注血管紧张素产生。
给DOCA-盐大鼠注射RBG可降低VE动物的血压并减少蛋白尿，但对输注血管紧张素的大鼠没有影响。此外，虽然两组高血压大鼠主动脉中超氧阴离子的产生量均高于对照组，但RBG仅使VE（DOCA-盐）动物的这些水平恢复正常。RBG对输注血管紧张素的大鼠没有作用。血管紧张素原的尿排泄量在VE介导的高血压中没有升高，但在输注血管紧张素的大鼠中确实增加。
MBG在VE大鼠高血压的发生中起重要作用，但在血管收缩模型中不起作用。RBG仅对VE介导的高血压有效。
