Early treatment with losartan effectively ameliorates hypertension and improves vascular remodeling and function in a prehypertensive rat model.
OBJECTIVE
Pharmacological treatment of prehypertension may ameliorate hypertension and improve vascular structure and function. This study investigated 1) whether early treatment with either losartan or amlodipine at the onset of prehypertension can prevent hypertension and 2) whether losartan and amlodipine equally improve vascular remodeling and function in a rat model of hypertension.


METHODS
Stroke-prone spontaneously hypertensive (SHRSP) rats were administered losartan, amlodipine or saline for 6 or 16weeks at the onset of prehypertension. Wistar-Kyoto rats were used as a control. All groups were observed for 40weeks. Systolic blood pressure was measured using the tail-cuff method. Vascular structure and function were determined by microscopy and vascular ring contractility assays, respectively. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassays. Angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression was measured by western blot.


RESULTS
Losartan effectively reduced progression from prehypertension to hypertension as well as vascular remodeling and improved vascular contractility in SHRSP rats. Long-term losartan (16weeks) had greater benefits than short-term (6weeks) treatment. Losartan increased Ang II and decreased Aldo levels in the serum and vessel walls of resistance vessels in a time-dependent manner. Losartan significantly decreased AT1R and increased AT2R vascular expression. Amlodipine had no effect on vascular AT1R and AT2R expression.


CONCLUSIONS
Losartan administered at the onset of prehypertension is more effective than amlodipine in ameliorating hypertension and improving vascular remodeling and function, which is likely mediated by the renin-angiotensin-aldosterone system.
Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, PR China.
De-Hua
DH
He
Department of Cardiology, The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, PR China.
Jin-Xiu
JX
Lin
Department of Cardiology, People's Hospital of Ningdu County, Ganzhou, Jiangxi, PR China.
Liang-Min
LM
Zhang
Fujian Institute of Hypertension, Fujian, PR China.
Chang-Sheng
CS
Xu
Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, PR China. Electronic address: xieqiangxiamen@163.com.
Qiang
Q
Xie
D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis; D066253:Vascular Remodeling / Q000187:drug effects*
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D000450:Aldosterone; D019808:Losartan
Amlodipine; Blood pressure; Losartan; Prehypertension; Vascular