Mechanical Pressure Unloading Therapy Reverses Thoracic Aortic Structural and Functional Changes in a Rat Model of Abdominal Aortic Constriction-Induced Arterial Hypertension

Objectives: Over time, uncontrolled high arterial blood pressure can lead to hypertensive cardiomyopathy and to a direct impairment of the blood vessel walls. In cases of pressure overload-induced cardiovascular diseases (aortic stenosis, hypertension) the elimination of the pressure overload, either by surgical intervention (aortic valve replacement/repair) or by medical intervention (antihypertensive therapy), could lead to the regression of pressure overload associated alterations, called myocardial reverse remodelling. However, data describing this process in the vasculature is limited. We studied the influence of a pressure unloading therapy on both the structural and functional alterations of the aorta in a rat model of abdominal aortic constriction-induced arterial hypertension.

Methods: Vascular function was studied using isolated thoracic aortic rings in an in vitro organ bath 12 weeks after abdominal aortic banding (AB 12-week). Age-matched animals were sham-operated to serve as controls (sham 12-week). An abdominal aortic debanding (DB) procedure was performed after the 6th experimental week (AB + DB 12-week). Additionally, the aortic morphometry was studied with hematoxylin & eosin stained sections and acid fuchsin-orange (AFOG) staining was performed to assess collagen deposition.

Results: Normalized to body weight, intima-media thickness and cross-sectional areas were significantly higher in the AB 12-week group compared with the sham 12-week group, and similar in the AB+DB 12-week and sham 12-week groups. Results from functional experiments showed that the AB 12-week group reacted with a significantly greater maximum contraction to phenylephrine when compared with the sham 12-week group (Sham 12-week 3.1 ± 0.2 g vs. AB 12-week 4.1 ± 0.1 g vs. AB+DB 12-week 2.6 ± 0.1 g, p < 0.05). Additionally, when compared with the sham 12-week group, the AB 12-week group demonstrated an impaired maximum endothelium-dependent vasorelaxation to acetylcholine (Sham 12-week 83 ± 1% vs. AB 12-week 66 ± 2% vs. AB+DB 12-week 78 ± 2%, p < 0.05). All these functional changes were significantly reduced by DB. AFOG staining confirmed collagen accumulation in both AB groups when compared with the age-matched sham groups. The DB significantly lowered the aortic collagen content.

Conclusion: We demonstrated that both structural and functional changes in the thoracic rat aorta, induced by pressure overload, regressed due to mechanical pressure unloading therapy.