Renal function in adult rats subjected to prenatal dexamethasone.
1. Prenatal dexamethasone leads to low birth weight and compromises organogenesis, but its effects on nephrogenesis in male and female rats have not yet been investigated extensively. Reduced renal mass may be responsible for hypertension and renal haemodynamic and morphological adjustments to maintain the glomerular filtration rate (GFR). Subsequently, these compensatory mechanisms determine glomerular sclerosis and irreversible reduction in GFR. When a high-protein diet is associated with reduced renal mass, it accelerates glomerular sclerosis and the decline in renal function. The aim of the present study was to evaluate whether rats subjected to prenatal dexamethasone and a high-protein diet during growth present a premature decline in renal function. 2. The number of nephrons and renal haemodynamics were estimated in Wistar rats fed a high-protein diet (40% protein) after weaning in offspring of dams treated with either dexamethasone (0.1 mg/kg per day) or its vehicle (control; physiological solution, 0.1 mL/kg per day) during gestation. 3. At 70 days of age, rat offspring were anaesthetized and prepared surgically for renal haemodynamic measurements. 4. Mean arterial pressure (MAP), renal blood flow (RBF) and GFR were measured using a blood pressure transducer, a flow probe and inulin clearance, respectively. 5. The number of nephrons was counted using the acid-maceration technique. 6. Dexamethasone during pregnancy induced a lower weight gain in the dams (65%; P < 0.0001) and a lower birth weight in both male and female offspring (14 and 13%, respectively; P < 0.01). 7. Compared with control, the number of nephrons in male rats was reduced by 13% (30 703 +/- 1262 vs 26 308 +/- 1305, respectively; P < 0.05), but was unaltered in female rats (23 197 +/- 553 vs 24 231 +/- 1009, respectively). 8. Male and female rats did not show any alteration in MAP. In addition, they did not show any alteration in renal vascular resistance, RBF, filtration fraction or GFR. 9. In conclusion, prenatally administered dexamethasone (0.1 mg/kg during the entire pregnancy) induced a low birth weight. The magnitude of the reduction in nephrogenesis in male offspring from mothers treated with dexamethasone was not sufficient to alter renal function (measured at 70 days), even when rats had been fed a high-protein diet.
Martins
João P C
JP
Department of Physiology and Pharmacology, Biological Science Center, Federal University of Pernambuco, Recife, PE, Brazil.
Monteiro
Josélia C
JC
Paixão
Ana D O
AD
D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight; D003907:Dexamethasone / Q000008:administration & dosage* / Q000633:toxicity*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology / Q000502:physiology*; D008297:Male; D009399:Nephrons / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012727:Sex Characteristics; D015430:Weight Gain / Q000187:drug effects
D005938:Glucocorticoids; D003907:Dexamethasone