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AT1 Receptor Blockade Abolishes Renal Injury in Salt‐Sensitive Female mRen2.Lewis Rats with Chronic COX‐2 Inhibition
Author(s) -
Yamaleyeva Liliya M.,
Westwood Brian M.,
Chappell Mark C.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a591-c
Subject(s) - losartan , endocrinology , medicine , blockade , proteinuria , blood pressure , angiotensin ii receptor type 1 , enalapril , cyclooxygenase , renin–angiotensin system , ace inhibitor , kidney , chemistry , angiotensin converting enzyme , receptor , enzyme , biochemistry
Cyclooxygenase 2 (COX‐2) inhibitors may cause nephropathy in women with hypertension and underlying renal disease. Female mRen2.Lewis rats (mRen) exhibit a marked increase in blood pressure and an augmented renal COX‐2 expression in response to a high salt (HS) diet. Moreover, chronic COX‐2 inhibition exacerbates hypertension, proteinuria, collagen deposition, as well as increases urinary thromboxane and PGE2 in the HS fed mRen. The current study determined whether concomitant AT1 receptor blockade with losartan (LOS, 20 mg/kg/day) is protective in female HS mRen treated with the COX‐2 inhibitor NS‐398 (1 mg/kg/day, 4wks). Although LOS markedly reduced SBP in both groups, pressure remained significantly higher in the NS‐398 treated rats [144.5±2.0 vs. 161.6±5.4 mmHg, p<0.01 n=6]. Despite the difference in blood pressure, the reduction in proteinuria [10.7±1.5 vs. 5.1±2.6, n=6] and the heart weight‐to‐body weight ratio [4.3±0.1 vs. 4.0±0.2, n=6] was similar following LOS treatment. These data demonstrate that blockade of the renin‐angiotensin system (RAS) confers renal and cardiac protective effects in this salt‐sensitive, COX‐2 inhibited model. Moreover, the complete attenuation of proteinuria with LOS suggests that the deleterious actions of COX‐2 inhibitors may involve the RAS. Supported by HL56973, HL51952.