TY - JOUR
T1 - Chronic vasodilation increases renal medullary PDE5A and α-ENaC through independent renin-angiotensin-aldosterone system pathways
AU - West, Crystal A.
AU - Shaw, Stefan
AU - Sasser, Jennifer M.
AU - Fekete, Andrea
AU - Alexander, Tyler
AU - Cunningham, Mark W.
AU - Masilamani, Shyama M.E.
AU - Baylis, Chris
PY - 2013/11/15
Y1 - 2013/11/15
N2 - 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 reninangiotensin-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 subunit of the epithelial sodium channel (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 αENaC 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 αENaC through the MR.
AB - 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 reninangiotensin-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 subunit of the epithelial sodium channel (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 αENaC 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 αENaC through the MR.
KW - Arterial underfilling
KW - Phosphodiesterase 5A
KW - α Subunit of the epithelial sodium channel
UR - http://www.scopus.com/inward/record.url?scp=84887603041&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00003.2013
DO - 10.1152/ajpregu.00003.2013
M3 - Article
C2 - 24068049
AN - SCOPUS:84887603041
SN - 0363-6119
VL - 305
SP - R1133-R1140
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 10
ER -