Enhanced adrenal renin and aldosterone biosynthesis during sodium restriction in TGR (mREN2)27

Abstract

The aim of the study was to investigate the relationships between tissue renin and the steroid production in the adrenal cortex during dietary sodium restriction in the transgenic rat (TGR) (mREN2)27. Thus the effects of a 1-wk low-sodium intake (0.04% NaCl) were studied in 5-wk-old male TGR (n = 33, systolic blood pressure = 151 +/- 3 mmHg) and in 24 age- and sex-matched outbred normotensive Sprague-Dawley (SD) rats. Measurements of plasma and tissue hormones were obtained at 0, 4, and 7 days of a low-sodium diet. Sodium restriction caused sustained increases of adrenal renin activity (from 28.5 +/- 3.5 to 87.5 +/- 4.5 ng.mg protein-1.h-1 on day 7) and of adrenal renin mRNA (+63 +/- 13 and +43 +/- 7% on days 4 and 7, respectively), whereas plasma renin activity (from 3.3 +/- 0.3 to 4.4 +/- 0.6 ng.ml-1.h-1) and renal renin activity (from 0.85 +/- 0.25 to 0.7 +/- 0.4 microgram.mg protein-1.h-1) did not change. The stimulation of the adrenal renin-angiotensin system was associated with a large increase of the aldosterone synthase cytochrome P-450 mRNA (+165 +/- 35 and +184 +/- 44%, on days 4 and 7) and of plasma aldosterone levels (from 125 +/- 32 to 338 +/- 59 pg/ml, P < 0.01). In SD rats, in spite of a more consistent increase in renal and circulating renin, mineralocorticoid production did not increase significantly. These results demonstrate that the exaggerated biosynthesis of aldosterone in TGR during sodium restriction is associated with an activation of renin in the adrenal cortex but not in the kidney.

Effects of Anesthesia on Plasma and Kidney ANG II Levels in Normotensive and ANG II-Dependent Hypertensive Rats

“…Therefore, it seems conceivable that normotensive rats and 2K1C hypertensive rats respond to thiopental anesthesia by substantial increases in PRA with subsequently increased circulating ANG II levels. This assumption is in line with fi ndings that PRA is markedly suppressed in TGR and ANG IIinfused rats and that PRA was not changed by dietary sodium restriction in TGR [13,16,23,39] . These facts probably account for the lower plasma ANG II in anesthetized salt-replete and salt-deplete TGR and ANG IIinfused rats when compared with normotensive rats and 2K1C Goldblatt hypertensive rats.…”

“…However, of special interest is the observation that ANG II concentrations in the nonclipped kidney from 2K1C Goldblatt hypertensive rats, when measured in samples harvested immediately after decapitation, are not only signifi cantly different from values observed in normotensive HanSD fed a NS diet -even though the renal renin content was consistently reported to be suppressed -but the nonclipped kidney also maintained its responsiveness in ANG II production to anesthesia and surgery [11,16] . These fi ndings together with our observation that kidney ANG II concentrations in conscious hypertensive TGR with suppressed intrarenal renin activity [23,39] , are elevated when compared with HanSD fed a NS diet, clearly demonstrate a dissociation between renal renin content and renal ANG II concentration. Taken together, these fi ndings strongly indicate that renal renin depletion is not automatically associated with kidney tissue ANG II reduction and suggest that, similar to 2K1C hypertensive rats, also in TGR a renin-independent mechanism may be responsible for the enhanced intrarenal formation of ANG II [3,6,9] .…”

Upregulation and intrarenal redistribution of heat shock proteins 90α and 90β by low-sodium diet in the rat

“…As expected, the LSD group presented a significant reduction of urinary excretion of sodium, fractional excretion of sodium, and osmolarity. This reduction in sodium excretion was accompanied by an important elevation of serum aldosterone, a result of the well-known activation of the RAAS during sodium restriction, as extensively reported by other authors (Tarjan et al 1980;Rubattu et al 1994;Jo et al 1996).…”

Control of Aldosterone Secretion: A Model for Convergence in Cellular Signaling Pathways

“…Although plasma renin and ANG II concentrations are low in these animals, aldosterone secretion is high, indicating that intra-adrenal production of renin can effectively stimulate the glomerulosa cells by stimulating local ANG II production (419). Sodium restriction also increases adrenal renin activity and mRNA in such transgenic rats (480). The observation that the AT 1 -type ANG II receptor antagonist DuP 753 attenuates K ϩ -stimulated and ACTH-stimulated aldosterone production (209) suggests that the intra-adrenal renin-angiotensin system functions as a local amplifier of systemic stimuli.…”