Angiotensin II Type 1 Autoantibody Induced Hypertension During Pregnancy Is Associated With Renal Endothelial Dysfunction

Background: Previous investigations suggested that agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) might mediate a hypertensive response through dysregulation of the endothelin-1 system. AT1-AA induced hypertension was attenuated by the AT1 receptor and/or endothelin-1 type A receptor antagonists. Objectives: This study was undertaken to determine if AT1-AA induced hypertension was associated with renal endothelial dysfunction. Methods: We compared the vascular reactivity of renal interlobar arteries from normal pregnant control rats and AT1-AA long-term infused pregnant rats in the presence and absence of endothelin type A (ETA) receptor antagonism. Renal endothelial function was tested using isolated renal interlobar arteries in a pressure myograph, which were exposed to acetylcholine or sodium nitroprusside. Results: Vasodilatory responses to the endothelial-dependent agonist acetylcholine were impaired in AT1-AA rats (74 [10]%) compared with normal pregnant controls (95 [5]%, P < 0.05). In the presence of ETA receptor antagonism, no differences were observed between controls or the AT1-AA treated group with regard to endothelial-dependent (acetylcholine) relaxation. Conclusion: AT1-AA induced hypertension during pregnancy was associated with disparate renal endothelial responses to acetylcholine. The difference in renal vascular responses between AT1-AA and normal pregnant rats was abolished by ET(A) receptor blockade. (Gend Med. 2011;8:184-188) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.