Changes in the composition of the thoracic aortic wall in spontaneously hypertensive rats treated with losartan or spironolactone.
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.
Han
Wei-Qing
WQ
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wu
Ling-Yun
LY
Zhou
Hai-Yan
HY
Zhang
Jia
J
Che
Zai-Qian
ZQ
Wu
Yong-Jie
YJ
Liu
Jian-Jun
JJ
Zhu
Ding-Liang
DL
Gao
Ping-Jin
PJ
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D003238:Connective Tissue / Q000737:chemistry / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004549:Elastin / Q000032:analysis / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D004232:Diuretics; D013148:Spironolactone; D003094:Collagen; D004549:Elastin; D019808:Losartan