scholarly journals Chronic vasodilation increases renal medullary PDE5A and α-ENaC through independent renin-angiotensin-aldosterone system pathways

2013 ◽  
Vol 305 (10) ◽  
pp. R1133-R1140 ◽  
Author(s):  
Crystal A. West ◽  
Stefan Shaw ◽  
Jennifer M. Sasser ◽  
Andrea Fekete ◽  
Tyler Alexander ◽  
...  
Keyword(s):  
Plasma Volume ◽  
Enzyme Inhibitor ◽  
Virgin Female ◽  
Normal Pregnancy ◽  
Female Rats ◽  
Plasma Volume Expansion ◽  
Renin Angiotensin Aldosterone System ◽  
Α Subunit ◽  
Renin Angiotensin

We have previously observed that many of the renal and hemodynamic adaptations seen in normal pregnancy can be induced in virgin female rats by chronic systemic vasodilation. Fourteen-day vasodilation with sodium nitrite or nifedipine (NIF) produced plasma volume expansion (PVE), hemodilution, and increased renal medullary phosphodiesterase 5A (PDE5A) protein. The present study examined the role of the renin-angiotensin-aldosterone system (RAAS) in this mechanism. Virgin females were treated for 14 days with NIF (10 mg·kg−1·day−1 via diet), NIF with spironolactone [SPR; mineralocorticoid receptor (MR) blocker, 200–300 mg·kg−1·day−1 via diet], NIF with losartan [LOS; angiotensin type 1 (AT1) receptor blocker, 20 mg·kg−1·day−1 via diet], enalapril (ENAL; angiotensin-converting enzyme inhibitor, 62.5 mg/l via water), or vehicle (CON). Mean arterial pressure (MAP) was reduced 7.4 ± 0.5% with NIF, 6.33 ± 0.5% with NIF + SPR, 13.3 ± 0.9% with NIF + LOS, and 12.0 ± 0.4% with ENAL vs. baseline MAP. Compared with CON (3.6 ± 0.3%), plasma volume factored for body weight was increased by NIF (5.2 ± 0.4%) treatment but not by NIF + SPR (4.3 ± 0.3%), NIF + LOS (3.6 ± 0.1%), or ENAL (4.0 ± 0.3%). NIF increased PDE5A protein abundance in the renal inner medulla, and SPR did not prevent this increase (188 ± 16 and 204 ± 22% of CON, respectively). NIF increased the α-subunit of the epithelial sodium channel (α-ENaC) protein in renal outer (365 ± 44%) and inner (526 ± 83%) medulla, and SPR prevented these changes. There was no change in either PDE5A or α-ENaC abundance vs. CON in rats treated with NIF + LOS or ENAL. These data indicate that the PVE and renal medullary adaptations in response to chronic vasodilation result from RAAS signaling, with increases in PDE5A mediated through AT1 receptor and α-ENaC through the MR.

Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic renal failure

1999 ◽  
Vol 96 (4) ◽  
pp. 427-430 ◽  
Author(s):  
M. BLUM ◽  
Y. WEISMAN ◽  
S. TURGEMAN ◽  
S. CABILI ◽  
Y. WOLLMAN ◽  
...  
Keyword(s):  
Renal Failure ◽  
Parathyroid Hormone ◽  
Chronic Renal Failure ◽  
Virgin Female ◽  
Normal Pregnancy ◽  
High Serum ◽  
Female Rats ◽  
Pregnant Rats ◽  
Serum Ipth ◽  
Immunoreactive Parathyroid Hormone

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20–21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100±18 pg/ml) and low calcitriol levels (10.6±4.3 pg/ml) compared with normal rats [N1: 14±2.5 pg/ml (P< 0.001) and 18.2±4.2 pg/ml (P< 0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2±5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4±8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87±17 pg/ml) and low calcitriol levels (9.3±1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.

Role of renin-angiotensin system in glucocorticoid hypertension in rats

1982 ◽  
Vol 243 (1) ◽  
pp. E48-E51 ◽  
Author(s):  
H. Suzuki ◽  
M. Handa ◽  
K. Kondo ◽  
T. Saruta
Keyword(s):  
Blood Pressure ◽  
Intravenous Injection ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Dependent Manner ◽  
Concurrent Administration ◽  
Angiotensin System ◽  
Renin Angiotensin

The role of the renin-angiotensin system in the regulation of the blood pressure of dexamethasone-treated rats (Dex) was evaluated using saralasin, an angiotensin II antagonist, and SQ 14225 (SQ) (d-3-mercapto-2-methylpropranoyl-1-proline), an angiotensin-converting enzyme inhibitor. During a 7-day period blood pressure rose 65 +/- 10 mmHg (P less than 0.001) in Dex with no significant changes in plasma renin activity. Concurrent administration of dexamethasone and SQ attenuated the elevation of blood pressure (P less than 0.05). In the conscious, freely moving state, intravenous injection of SQ (10, 30, 100 micrograms/kg) reduced blood pressure of DEX in a dose-dependent manner (P less than 0.05). Also, intravenous injection of saralasin (10 micrograms.kg-1 . min-1) reduced blood pressure significantly (P less than 0.01). Bilateral nephrectomy abolished the effects of saralasin and SQ on blood pressure in Dex. These results indicate that the elevation of blood pressure in DEX depends partially on the renin-angiotensin system.

Role of adrenal renin-angiotensin system in the control of aldosterone secretion in sodium-restricted rats

2000 ◽  
Vol 278 (6) ◽  
pp. E1027-E1030 ◽  
Author(s):  
Giuseppina Mazzocchi ◽  
Ludwik K. Malendowicz ◽  
Anna Markowska ◽  
Giovanna Albertin ◽  
Gastone G. Nussdorfer
Keyword(s):  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Zona Glomerulosa ◽  
Normal Diet ◽  
Angiotensin Ii Receptor ◽  
Aldosterone Secretion ◽  
Angiotensin System ◽  
Renin Angiotensin

This study examined the effect of the pharmacological manipulation of adrenal renin-angiotensin system (RAS) on aldosterone secretion from in situ perfused adrenals of rats kept on a normal diet and sodium restricted for 14 days. Neither the angiotensin-converting enzyme inhibitor captopril nor the nonselective angiotensin II receptor antagonist saralasin and the AT1 receptor-selective antagonist losartan affected basal aldosterone output in normally fed rats. In contrast, they concentration dependently decreased aldosterone secretion in sodium-restricted animals, with maximal effective concentration ranging from 10− 7 to 10− 6 M. Captopril (10− 6 M), saralasin (10− 6 M), and losartan (10− 7 M) counteracted aldosterone response to 10 mM K+ in sodium-restricted rats but not in normally fed animals. Collectively, these findings provide evidence that adrenal RAS plays a role in the regulation of aldosterone secretion, but only under conditions of prolonged stimulation of zona glomerulosa probably leading to overexpression of adrenal RAS.

scholarly journals Increased renal α-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy

2010 ◽  
Vol 299 (5) ◽  
pp. R1326-R1332 ◽  
Author(s):  
Crystal West ◽  
Zheng Zhang ◽  
Geoffrey Ecker ◽  
Shyama M. E. Masilamani
Keyword(s):  
Plasma Volume ◽  
Late Pregnancy ◽  
Normal Pregnancy ◽  
In Vivo Studies ◽  
Volume Status ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Mineralocorticoid Receptor Antagonist ◽  
The Difference

Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na+/H+ exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy ( days 18–20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (UNaV postbenzamil-UNaV postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

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