Changes in the Composition of the Thoracic Aortic Wall in Spontaneously Hypertensive Rats Treated With Losartan or Spironolactone

Abstract

1. In the present study, we compared the elastin and collagen content of thoracic aortic medial and adventitial layers from Wistar-kyoto (WKY) and spontaneously hypertensive rats (SHR). In addition, the effects of losartan, an angiotensin II receptor antagonist, and spironolactone, a mineralocorticoid receptor antagonist, on collagen and elastin content were determined. 2. Prehypertensive (4-week-old) and hypertensive (16-week-old) SHR were randomly divided into three groups treated with either 0.9% NaCl, losartan (20 mg/kg per day) or spironolactone (200 mg/kg per day). Prehypertensive and hypertensive SHR were treated for 12 and 16 weeks, respectively. Age-matched WKY rats were not treated with NaCl, losartan or spironolactone and served as the control group. 3. The medial and adventitial layers of the thoracic aorta were composed mainly of elastin and collagen, respectively, in both SHR and WKY rats. Compared with WKY rats, SHR exhibited greater collagen and elastin content in the media, but decreased collagen and elastin content in the adventitial layer. Both medial and adventitial collagen and elastin content increased significantly with age in both strains and was greater in 32-week-old rats compared with 16-week-old rats. Spironolactone treatment decreased collagen content in the media of thoracic aortas from prehypertensive SHR, whereas losartan decreased collagen content in the media of aortas from hypertensive SHR. In contrast, neither spironolactone nor losartan had any effect on adventitial collagen content in prehypertensive and hypertensive SHR. Medial collagen and elastin were positively related to pulse pressure (PP), but there was no correlation between adventitial mass or collagen content and PP or mean arterial pressure in untreated and treated SHR and WKY rats. 4. In conclusion, the composition of the medial and adventitial layers of the thoracic aorta differs and treatment of SHR with losartan and spironolactone decreases collagen content when delivered at the hypertensive or prehypertensive stage, respectively. However, neither drug has any effect on adventitial collagen content in SHR.

Different biomechanical properties of medial and adventitial layers of thoracic aorta in Wistar-Kyoto and spontaneously hypertensive rats

“…The present study showed that maximum stiffness was reduced after adventitial removal in WKY and SHR at both ages, indicating that adventitial layers play a contributory role in vascular biomechanical properties. This finding is consistent with our previous study showing that there were abundant densely distributed collagen in Sirius Red Staining, and hydroxyproline measurement showed that adventitial layer collagen was comparable to that in the medial layer [12] . These finding indicated that adventitial layer might be a pharmacological target in the prevention and treatment of cardiovascular diseases.…”

“…In 2-kidney 1-clip hypertensive rats, carotid arteries were stiffer after 9 and 24 weeks, but no stiffening had occurred at 1 and 5 weeks after renal artery clipping [23] . In consistent with these above findings, the present study showed that there was no significant difference between SHR and WKY at the age of 16 and 32 week in terms of elastic stiffness and maximum stiffness in intact thoracic aorta, or in thoracic media (without adventitia), which is consistent with our previous finding that elastin : collagen ratio in thoracic media and adventitia was not changed in SHR and WKY, although there is significant medial remodeling in 16-and 32-week old SHR compared with age-matched WKY including increased mass, collagen and elastin content, thoracic adventitial collagen [12] . These results indicated that elastin : collagen ratio may be the determinant of vascular stiffness [24][25][26] .…”

“…Our previous study showed that thoracic adventitial layer contained as much collagen as that of thoracic media, and that collagen was densely distributed in adventitial layer in Sirius Different biomechanical properties of medial and adventitial layers of thoracic aorta in Wistar-Kyoto and spontaneously hypertensive rats Red Staining, indicating that adventitial layer might play a role in the biomechanical characteristics of thoracic aorta [12] . Importantly, the thoracic medial layer underwent different remodeling from that of thoracic adventitia in spontaneously hypertensive rats (SHR) compared with normotensive WistarKyoto (WKY) rats [12] .…”

“…Importantly, the thoracic medial layer underwent different remodeling from that of thoracic adventitia in spontaneously hypertensive rats (SHR) compared with normotensive WistarKyoto (WKY) rats [12] . To elucidate the biomechanical contribution of adventitial layer and the possible alteration in hypertensive objectives, we examined the load-stain relationships of the intact thoracic aorta and thoracic media (adventitial layer was removed) in SHR and WKY.…”

Quantification of Elastin, Collagen and Advanced Glycation End Products as Functions of Age and Hypertension

“…They found that both collagen and elastin synthesis (as revealed by specific hydroxyproline activity) exceeded WKR control levels in the prehypertensive period (at the age of 4 weeks ), decreased in the development of hypertension (to the age of 14-16 weeks), and increased again in the period of the established hypertensive state (beyond the age of 16 weeks). Several studies showed that this second increase in connective tissue proteins may be prevented, depending on the choice of antihypertensive therapy (Tsoporis et al, 1998;Han et al, 2009).…”