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(Circulation. 2001;104:2391.)
© 2001 American Heart Association, Inc.

Brief Rapid Communications

Hypertension Does Not Account for the Accelerated Atherosclerosis and Development of Aneurysms in Male Apolipoprotein E/Endothelial Nitric Oxide Synthase Double Knockout Mice

Jiqiu Chen, MD^*; Peter J. Kuhlencordt, MD^*; Joshua Astern, BS; Robert Gyurko, DDS, PhD; Paul L. Huang, MD, PhD

From the Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Paul L. Huang, MD, PhD, Cardiovascular Research Center, Massachusetts General Hospital East, 149 East 13th Street, Charlestown, MA 02129. E-mail HuangP{at}helix.mgh.harvard.edu

Background— Apolipoprotein E (apoE)/endothelial nitric oxide synthase (eNOS) double knockout (DKO) mice demonstrate accelerated atherosclerosis and develop abdominal aortic aneurysms and aortic dissection, suggesting a role for eNOS in suppressing atherogenesis. To test whether accelerated atherosclerosis and aortic aneurysms were due to hypertension, we administered hydralazine to male apoE/eNOS DKO mice to reduce blood pressure.

Methods and Results— Male apoE/eNOS DKO mice were treated with hydralazine in their drinking water (250 mg/L) using a dose that lowers the blood pressure to levels seen in apoE KO mice. The mice were fed a Western-type diet for 16 weeks, and lesion formation was assessed by inspection of the vessel and staining with Sudan IV. Hydralazine-treated, normotensive male apoE/eNOS DKO mice developed increased aortic lesion areas (30.0±2.8%, n=11) compared with male apoE KO mice (14.6±0.8%, n=7). The extent of lesion formation was not significantly different from male apoE/eNOS DKO mice that were not given hydralazine (28.3±3.1%, n=9). Four of 11 hydralazine-treated male apoE/eNOS DKO mice developed abdominal aortic aneurysms.

Conclusions— Hypertension is not required for the accelerated atherosclerosis seen in apoE/eNOS DKO animals, and control of hypertension during a 16-week period does not prevent aortic aneurysm formation.

Key Words: arteriosclerosis • nitric oxide synthase • aneurysm • hypertension • hydralazine

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