Renal mRNA response to reduced perfusion pressure conserved despite denervation in mature ovine fetuses.

We hypothesized that renal denervation in mature ovine fetuses reduces renin mRNA response to 24 h of reduced renal perfusion pressure (RPP). Seven occluder (O) (132.4 +/- 1.2 days gestation) and six control (C) (131.5 +/- 1.2 days gestation) fetuses underwent left renal denervation. Postoperatively, O fetuses experienced 24 h of reduced RPP by suprarenal aortic occlusion. Femoral arterial blood pressure (FAB) and plasma active renin (pARC) and prorenin (pPRC) concentrations were obtained hourly for 6 h and at h 23 and 24. Renin mRNA was measured by RNase protection assay. We quantitated renin containing glomeruli by immunocytochemistry. Variables were compared by ANOVA. Mean O group FAB reduction from baseline was -6.60 +/- 0.41 mmHg. pARC and pPRC increased with occlusion, renal ARC and renal PRC did not increase with occlusion. No effect in renin mRNA or number of positive glomeruli was noted with denervation in the basal state; however, significant increases were noted in response to RPP irrespective of innervation status. In conclusion, 24 h or reduced RPP in mature ovine fetus increases renal renin mRNA and the immunocytochemical expression of renin. This response is conserved despite denervation.

Active renin, prorenin, and renin gene expression after reduced renal perfusion pressure in term ovine fetuses.

We studied the pattern of plasma active renin concentration (ARC), prorenin concentration (PRC), renal renin concentration, and the renin mRNA levels in ovine fetuses subjected for 24 h to reduced renal perfusion pressure (RPP). The results obtained in five animals (133.8 +/- 1.4 days of gestation) in which RPP was reduced by 10 mmHg were compared with those in seven control fetuses (130.3 +/- 0. 8 days of gestation) without pressure reduction. Plasma samples were obtained before and at intervals of 24 h after initiating reduced RPP. The plasma ARC increased within 60 min of reduced RPP, reaching a maximum (13.0 +/- 4.7 vs. 115.7 +/- 23.8, P < 0.01) at 3 h. The ARC then declined toward control values. In contrast, plasma PRC did not increase consistently until 4 h into reduced RPP, with maximal levels at 24 h (8.2 +/- 2.4 vs. 87.7 +/- 21.9, P = 0.016). Within the kidney PRC, but not ARC, increased significantly, by 2.5-fold. Reduced RPP also increased renal renin mRNA levels (P = 0.004). We conclude that a chronic reduction in RPP in the near-term ovine fetus increases renal PRC and is associated with increased plasma prorenin levels. The data suggest that the conversion of prorenin to active renin is an important regulation point of the renin ANG system during development.

Gaucher's disease in pregnancy.

Gaucher's disease is an autosomal recessive lysosomal storage disease, resulting from a deficiency of the enzyme glucocerebrosidase, important for the physiologic recycling of cell membrane lipids. The clinical symptoms and disease presentations of Gaucher's disease are heterogeneous, including hepatosplenomegaly, bone "crisis" and fracture, anemia, thrombocytopenia and in some forms, rapid neurological decompensation. Similarly, the genetic variability of Gaucher's disease is diverse, and in some aspects affects phenotypic expression. Type 1 Gaucher's disease, however, usually present with less severe symptoms, at more advanced age, and is particularly amenable to enzyme replacement therapy with alglucerase. In type 1 patients with Gaucher's disease reproductive age is commonly reached and childbearing frequently desired with need for appropriate prenatal diagnosis, counseling and careful obstetrical surveillance. Although pregnancy concurrent with Gaucher's disease has been reported in the medical literature, only one small series of alglucerase treated Gaucher's disease during pregnancy exists. Without treatment, pregnancy concurrent with Gaucher's disease has several risks including an increased severity of anemia and thrombocytopenia that can potentiate postpartum bleeding, significant increases in organomegaly and possibly an increased spontaneous abortion rate. It is yet to be shown whether alglucerase reduces the risk of these complications during pregnancy and whether its use has any adverse effect on fetal development.