Effect of renal denervation on prenatal programming of hypertension and renal tubular transporter abundance.
Prenatal glucocorticoids are often administered to pregnant women to accelerate pulmonary maturation. We have demonstrated that administration of dexamethasone during specific periods of pregnancy in the rat causes hypertension in the offspring when they are studied as adults. The purpose of the present study was to determine whether the hypertension due to prenatal dexamethasone was mediated by renal nerves. We administered dexamethasone to rats daily for 4 days between days 15 and 18 of gestation. Rats underwent bilateral renal denervation or sham operation at 6 wk of age, and blood pressure was measured at 8 wk of age. Prenatal dexamethasone in the sham operation group resulted in an increase in blood pressure compared with vehicle-treated sham controls (134 +/- 3 vs. 145 +/- 3 mmHg, P < 0.05). Renal denervation did not affect blood pressure significantly in the prenatal vehicle-treated control group but resulted in normalization in blood pressure in the prenatal dexamethasone group and (130 +/- 3 and 128 +/- 5 mmHg, respectively). Prenatal dexamethasone increased type 3 Na+/H+ exchanger (NHE3), Na+K+-2Cl(-) cotransporter (NKCC2), and Na+-Cl(-) cotransporter (NCC), but not alpha-, beta-, and gamma-epithelial Na+ channel (ENaC) protein abundance compared with controls. The increase in NHE3, NKCC2, and NCC protein abundance by prenatal dexamethasone was not seen in 8-wk-old rats 2 wk after renal denervation. Renal denervation did not affect NHE3, NKCC2, and NCC protein abundance in prenatal vehicle-treated animals. This study is consistent with renal nerves playing a role in mediating the hypertension by prenatal programming by dexamethasone.
Dagan
Amit
A
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9063, USA.
Kwon
H Moo
HM
Dwarakanath
Vangipuram
V
Baum
Michel
M
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003714:Denervation; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000209:etiology*; D007668:Kidney / Q000294:innervation*; D007684:Kidney Tubules / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D049992:Sodium Chloride Symporters / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1
C578716:Slc12a1 protein, rat; C000613387:Slc9a3 protein, rat; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D003907:Dexamethasone