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Parallel changes in the urinary excretion of ANG II and angiotensinogen and kidney ANG II levels in slowly progressive ANG II‐dependent hypertension (1136.20)
Author(s) -
Sigmon David,
Seth Dale,
Sato Akemi,
Davis Porcha,
Navar L,
Mitchell Kenneth
Publication year - 2014
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.28.1_supplement.1136.20
Subject(s) - endocrinology , medicine , excretion , kidney , urinary system , renin–angiotensin system , angiotensin ii , chemistry , blood pressure
Previous studies have demonstrated that the urinary excretion of ANG II and AGT, and kidney ANG II levels are markedly elevated in ANG II‐dependent malignant hypertension associated with marked renal injury. The present study was performed to determine the temporal changes in urinary ANG II and AGT excretion and kidney ANG II levels in a model of slowly progressive ANG II‐dependent hypertension in Cyp1a1‐Ren2 transgenic rats with inducible expression of the Ren2 renin gene. Male Cyp1a1‐Ren2 rats (n=6/group) were induced to develop slowly progressive ANG II‐dependent hypertension by dietary administration of indole‐3‐carbinol (I3C, 0.15% wt/wt) for 14 days. Conscious systolic blood pressures (SBP) increased from 140±8 to 176±9 mmHg (P<0.05) by day 4 of I3C induction, whereas the urinary excretion of ANG II and AGT both increased by day 3 of I3C induction (32.1±3 to 64.8±6 fmol/hr and from 123±25 to 437±75 ng/day, P<0.05 in both cases). Both urinary ANG II and AGT excretion continued to increase (P<0.01) and averaged 120±5 fmol/hr and 1384±514 ng/day, respectively, by day 13 of induction. Similarly, kidney ANG II levels were increased by day 13 of induction (1042±219 vs. 349±96 fmol/g, P<0.05). SBP, urinary ANG II and AGT excretion and kidney ANG II levels promptly decreased to control levels following termination of dietary I3C administration (to 127±2 mmHg, 60±5 fmol/hr, 83±34 ng/day, and 473±185 fmol/g, respectively, P<0.01 in all cases). The present findings demonstrate that the urinary excretion of ANG II and AGT increases progressively, and that total kidney ANG II levels are increased, following induction of ANG II‐dependent hypertension and decrease within 3 days to control levels following termination of dietary I3C administration. The data also indicate that the intratubular generation of ANG II increases progressively following induction of ANG II‐dependent hypertension and decreases promptly to control levels following termination of induction of ANG II‐dependent hypertension. Grant Funding Source : 5P30GM103337