Influence of estrogen depletion and salt loading on renal angiotensinogen expression in the mRen(2).Lewis strain.
The mRen(2).Lewis (mRen2) strain is an ANG II-dependent model of hypertension expressing marked sex differences in blood pressure and tissue injury that also exhibits estrogen and salt sensitivity. Because estrogen and salt influence angiotensinogen (AGT), circulating and renal expression of the protein were assessed in the mRen2 using a sensitive and specific ELISA. Hemizygous female and male mRen2 were placed on normal (1% NaCl, NS)- or high (8% NaCl, HS)-salt diets from 5 to 15 wk of age while a separate NS cohort was ovariectomized (OVX). The OVX mRen2 exhibited higher blood pressure (184 +/- 6 vs. 149 +/- 5 mmHg, n = 6), a 16-fold increase in urinary AGT (uAGT) (0.2 +/- 0.02 vs. 0.01 +/- 0.01 microg x kg(-1) x day(-1), P < 0.01), but no change in proteinuria (PROT). Excretion of AGT was correlated with blood pressure and PROT in the female groups. The HS diet led to higher blood pressure (224 +/- 8 mmHg), a 180-fold increase in uAGT (1.8 +/- 0.2 microg x kg(-1) x day(-1)), and increased PROT (98 +/- 9 vs. 7 +/- 1 mg x kg(-1) x day(-1)). Compared with females, NS males expressed higher excretion of uAGT (3.0 +/- 0.4 microg x kg(-1) x day(-1)) and PROT (32 +/- 5 mg x kg(-1) x day(-1)); both were increased eightfold with HS (uAGT: 23 +/- 3 microg x kg(-1) x day(-1); PROT: 285 +/- 28 mg x kg(-1) x day(-1)) without a change in blood pressure. Although uAGT was markedly higher in the OVX and HS groups, neither renal cortical AGT mRNA or protein expression was increased. Moreover, AGT release in cortical slices was similar for the NS and HS females. We conclude that the increase in uAGT with estrogen depletion or HS likely may be a biomarker for glomerular damage reflecting filtration of the circulating protein in the mRen2.
Cohen
Jonathan A
JA
Hypertension and Vascular Research Center, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157-1095, USA.
Lindsey
Sarah H
SH
Pirro
Nancy T
NT
Brosnihan
K Bridget
KB
Gallagher
Patricia E
PE
Chappell
Mark C
MC
D000808:Angiotensinogen / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D010052:Ovariectomy; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics*; D012737:Sex Factors; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013997:Time Factors; D015854:Up-Regulation
D015415:Biomarkers; D004967:Estrogens; D012333:RNA, Messenger; C473112:Ren2 protein, mouse; D017673:Sodium Chloride, Dietary; D000808:Angiotensinogen; D012083:Renin
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