title: Aldosterone receptor antagonism exacerbates intrarenal angiotensin II augmentation in ANG II-dependent hypertension.
abstract: Effects of aldosterone receptor (AR) blockade with eplerenone (epl) on renal Na(+) excretion, arterial blood pressure, intra-adrenal and renal ANG II, and plasma aldosterone levels during ANG II-dependent hypertension were evaluated. Rats from one cohort (n = 10/group) 1) control, 2) control + epl (25 mg/day), 3) ANG II (60 ng/min), and 4) ANG II + epl were maintained in metabolic cages for 28 days for daily urine collections. Systolic blood pressure (SBP) was measured weekly by tail-cuff. In a second cohort (n = 12/group), daily SBP was measured by telemetry (n = 6 rats/group) 1) control, 2) ANG II, and 3) ANG II + epl. A diet containing epl (0.1%) was provided after 1 wk of ANG II infusion. Direct monitoring of BP by telemetry showed that epl delayed the onset of the increase in SBP by 2 days and slightly reduced SBP (186 +/- 6 vs. 177 +/- 8 mmHg). Epl transiently increased Na(+) excretion within 24 h of treatment in both normo- and hypertensive rats; however, balance was reestablished within 5 days suggesting that alternative mechanisms for conserving Na(+) are activated. Cortical alpha-epithelial Na(+) channel content (alpha-ENaC) was not altered after 21 days of epl treatment. Epl exacerbated the ANG II-mediated increases in intrarenal ANG II (226 +/- 16 vs. 365 +/- 38 fmol/g) and further increased intra-adrenal ANG II (3.9 +/- 0.3 vs. 8.2 +/- 0.9 fmol/mg) and aldosterone (255 +/- 55 vs. 710 +/- 87 pmol/mg) content. Exacerbation of intrarenal ANG II levels likely contributes to the maintenance of alpha-ENaC protein content and thus Na(+) reabsorption, which helps explain the ineffectiveness of AR blockade in reducing SBP in ANG II-infused models of hypertension.
authors: Department of Renal Physiology, Tulane University Health Science Center, New Orleans, Louisiana, USA. rortiz@ucmerced.edu
authors: Rudy M
authors: RM
authors: Ortiz
authors: Miguel L
authors: ML
authors: Graciano
authors: Dale
authors: D
authors: Seth
authors: Mouhamed S
authors: MS
authors: Awayda
authors: L Gabriel
authors: LG
authors: Navar
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology; D004573:Electrolytes / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006400:Hematocrit; D006728:Hormones / Q000097:blood; D006977:Hypertension, Renal / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood / Q000378:metabolism / Q000652:urine; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D004573:Electrolytes; D053503:Epithelial Sodium Channels; D006728:Hormones; D000451:Mineralocorticoid Receptor Antagonists; D000804:Angiotensin II; D012965:Sodium Chloride; D012964:Sodium