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KMID : 0648320090150030010
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Journal of The Korean Society of Hypertension
2009 Volume.15 No. 3 p.10 ~ p.17
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The Effects of Rosiglitazone on Endothelin and the Atrial Natriuretic Peptide System in Deoxycorticosterone acetate-Salt Hypertensive Rats
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Bae Eun-Hui
Kim In-Jin
Ma Seong-Kwon
Lee Jong-Un
Kim Soo-Wan
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Abstract
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Background: We investigated whether the antihypertensive effects of rosiglitazone (RGT) are associated with the altered regulation of endothelin (ET) and atrial natriuretic peptide (ANP) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats.
Methods: The rats were implanted with DOCA strips (200 mg/kg) 1 week after the rats underwent unilateral nephrectomy. Two weeks after DOCA implantation, the DOCA-salt rats were randomly divided into 2 groups to receive the control diet with or without RGT (10mg/kg/day) for another 2 weeks. The protein expressions of aquaporins (AQPs), sodium transporters and neutral endopeptidase (NEP) were determined in the kidneys by performing semiquantitative immunoblotting. The mRNA expressions of ET-1 and ANP were determined by real-time polymerase chain reaction.
Results: In the DOCA-salt rats, the systolic blood pressure was markedly increased compared to that of the controls, and this was associated with an increased ET-1 mRNA expression in the aorta. The creatinine clearance and urine osmolarity were decreased, while the urinary excretion of sodium was increased. The protein expressions of NHE3, Na,K-ATPase and NKCC2, as well as AQP1 and AQP2, were decreased. RGT treatment counteracted the dysregulation of ET-1, AQPs and the sodium transporters, along with improving the renal function and attenuating the high blood pressure in the DOCA-salt hypertensive rats. The ANP expression was increased in the kidneys from the DOCA-salt hypertensive rats, as compared to that of the controls, while the NEP expression was decreased. RGT treatment prevented the upregulation of ANP and it attenuated the downregulation of the NEP expression in the kidney from the DOCA-salt rats.
Conclusions: RGT treatment decreased the blood pressure and improved the renal function in the DOCA-salt rats. Up-regulation of the mRNA expression of ET-1 in the aorta plays a role in the pathogenesis of hypertension in DOCA-salt rats. Down regulation of AQPs and sodium transporters may induce natriuresis and diuresis. Down-regulation of NEP and the increased ANP activity in the kidney play a compensatory role against the development of hypertension, which was counteracted by RGT treatment.
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KEYWORD
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Rosiglitazone, DOCA-salt, AQP, sodium transporters, ANP
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