Effect of pravastatin on nephroprotection in deoxycorticosterone acetate-salt hypertensive rats.
OBJECTIVE
Endothelin-1 (ET-1) has been implicated in the pathogenesis of renal impairment. The current study was undertaken to assess the effect of pravastatin on the progression of renal impairment in deoxycorticosterone acetate (DOCA)-salt hypertensive rats.


METHODS
Four weeks after the start of DOCA-salt treatment and uninephrectomization, male Wistar rats were treated with one of the following therapies for 8 weeks: vehicle; a nonselective endothelin receptor antagonist bosentan; pravastatin; or hydralazine.


RESULTS
Treatment with bosentan or pravastatin was associated with reductions in blood pressure and renal medullary hydroxyproline content, and improvement in glomerular filtration rate, urinary protein excretion, macrophage infiltration, tubular injury, and vascular injury, but not glomerulosclerosis. The renal medullary ET-1 protein levels and preproET-1 mRNA assessed by western blotting and real-time quantitative reverse transcription-PCR were significantly decreased (both P < 0.001) in the pravastatin-treated rats compared with vehicle, which was also confirmed by immunohistochemical analysis. However, there were no significant differences of ET-1 levels in the renal cortex among the DOCA-salt groups. The nephroprotective effects of pravastatin were not associated with its antihypertensive action because hydralazine despite reducing blood pressure failed to improve renal function and disorder.


CONCLUSIONS
These results suggest a crucial role of renal endothelin system in the pathogenesis of renal functional and structural alterations in the DOCA-salt hypertensive rats. Pravastatin administration ameliorates the impairment of renal function and structures by attenuating medullary ET-1 expression, independent of systemic blood pressure.
Kang
Chih-Sen
CS
Department of Cardiovascular Medicine, Min-Sheng General Hospital, Taoyuan, Taipei, Taiwan.
Chang
Nen-Chung
NC
Chang
Shen-Tien
ST
Lin
Chih-Chan
CC
Lee
Tsung-Ming
TM
D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D017931:DNA Primers; D003900:Desoxycorticosterone / Q000009:adverse effects*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009929:Organ Size; D017035:Pravastatin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*
D017931:DNA Primers; D019332:Endothelin-1; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone; D017035:Pravastatin