Effects of rosiglitazone on heat shock protein and the endothelin system in deoxycorticosterone acetate-salt hypertensive rats.
The deoxycorticosterone acetate (DOCA)-salt rat is known as a model of volume dependent hypertension and characterized by increased cardiac endothelin-1 (ET-1) content. Recently, it has been reported that rosiglitazone (RGT), a peroxisome proliferator-activated subtype gamma receptor agonist, shows blood pressure lowering effect. We investigated whether DOCA-salt hypertension is associated with altered expression of heat shock proteins (HSP) and ET-1 in the heart, aorta, and kidney, and whether RGT changes HSP expression and ET-1 in association with its blood pressure lowering effect. Two weeks after the silastic DOCA (200 mg/kg) strips implantation, DOCA-salt rats were randomly divided to receive control diet with or without RGT (10 mg/kg/day) for another 2 weeks. The mRNA expression of ET-1 was determined by real time polymerase chain reaction. The expression of HSP was determined by semiquantitative immunoblotting. In DOCA-salt rats, systolic blood pressure was markedly increased, while creatinine clearance decreased. RGT treatment attenuated high blood pressure and decreased creatinine clearance in DOCA-salt rats. The mRNA expression of ET-1 was increased in DOCA-salt rats compared to controls, which was counteracted by RGT treatment. The protein expression of HSP70, HSP32, and HSP25 was increased in the kidney and heart in DOCA-salt rats, which was attenuated by RGT treatment in the kidney, but not in the heart. In conclusion, increased expression of ET-1 may play a role in the pathogenesis of hypertension in DOCA-salt rats, which was counteracted by the treatment of RGT. Up-regulation of HSP70, HSP32, and HSP25 in the kidney and heart may play a role in organ protection against a variety of stresses.
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
Eun Hui
EH
Bae
Department of Physiology, Chonnam National University Medical School, Gwangju, Korea.
In Jin
IJ
Kim
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
Jeong Woo
JW
Park
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
Seong Kwon
SK
Ma
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
Ki Chul
KC
Choi
Department of Physiology, Chonnam National University Medical School, Gwangju, Korea.
Jongun
J
Lee
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
Soo Wan
SW
Kim
deoxycorticosterone acetate-salt; endothelin-1; heat-shock proteins; rosiglitazone