Hypertension does not account for the accelerated atherosclerosis and development of aneurysms in male apolipoprotein e/endothelial nitric oxide synthase double knockout mice.
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.


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.
Chen
J
J
Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Kuhlencordt
P J
PJ
Astern
J
J
Gyurko
R
R
Huang
P L
PL
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001014:Aortic Aneurysm / Q000209:etiology* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000150:complications*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
D000959:Antihypertensive Agents; D001057:Apolipoproteins E; D006830:Hydralazine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse