Objectives: Sustained elevations in arterial blood pressure can induce maladaptive changes in
blood vessel walls. However, data describing time-course changes in aortic vascular
endothelial function after aortic constriction-induced arterial hypertension and the
reverse remodeling process after a mechanical pressure unloading therapy in the vasculature
are limited. We investigated time-course of endothelial functional changes in the
aorta in response to pressure overload and to a pressure unloading therapy, without
the influence of anti-hypertensive drugs, in a hypertensive rat model.
Methods: The aortic morphometry and fibrosis of the aortic wall were studied. Acetylcholine
(ACh) induced (endothelium-dependent) vasorelaxation was investigated in an in vitro
organ bath system using phenylephrine precontracted thoracic aortic rings 6, 12, or
18 weeks after abdominal aortic banding (AB 6W, AB 12W, or AB 18W) and after an aortic
debanding (DB) procedure performed at week 6 and week 12 of aortic banding (AB + DB
12W or AB + DB 18W). Age-matched animals were sham-operated (sham 6W, sham 12W or
sham 18W) to serve as controls.
Results: AB significantly increased systolic, diastolic and pulse pressures, intima-media
thickness, wall area and aortic collagen content, and decreased maximum relaxation
Rmax to ACh in 6, 12, 18 weeks compared with age matched controls. Structural changes
and decreased Rmax to ACh were similar in the AB 6W and AB 12W. However, sustained pressure overload
for 18W significantly decreased endothelium-dependent relaxation to ACh further when
compared to AB 6W and AB 12W (AB 18W 36 ± 3 vs. AB 6W 67 ± 3 vs. AB 12W 62 ± 4%, p < 0.05). Decreased blood pressures, ameliorated structural changes, and improved
endothelial function were observed in the AB + DB 12W and AB + DB 18W compared with
their respective AB groups (Rmax to ACh: AB + DB 12W 78 ± 2 vs. AB 12W 62 ± 4%; AB + DB 18W 51 ± 3 vs. AB 18W 36 ± 3%,
p < 0.05).
Conclusions: We showed similar endothelial dysfunction after 6 and 12 weeks of pressure overload.
However, sustained pressure overload for 18 weeks was associated with further endothelial
dysfunction. Diminishing the pathological stimulus, arterial hypertension itself,
improves endothelial dysfunction after 12 and even 18 weeks of abdominal aortic constriction.