Time Course of Changes in Aortic Endothelial Function in Hypertensive Rats: Effects of a Mechanical Pressure Unloading Therapy

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 R_max to ACh in 6, 12, 18 weeks compared with age matched controls. Structural changes and decreased R_max 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 (R_max 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.

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