Jennifer Manning

Low birth weight-associated adult hypertension in the rat.

Abstract Epidemiological surveys have suggested that intrauterine growth retardation is a risk factor for the development of hypertension in later life. A rat model of intrauterine growth retardation, induced by maternal low-protein diet during the second half of pregnancy, was used to study the relationship between birth weight and adult hypertension. The offspring were born at term and were allowed to nurse normally until weaned to standard chow at 4 weeks of age. They had 15% lower birth weights than control offspring, with complete catch-up growth by age 4 weeks. Both females and males developed progressively worsening hypertension beginning at 8 weeks. The 11-month survival rate was 69% versus 100% in control animals. During the early stages of the hypertension, plasma creatinine was normal, plasma sodium concentration was slightly higher than that of control animals, plasma renin activity was suppressed, and the males had mild proteinuria. Renal function remained normal throughout the 11-month observation period, but plasma renin activity gradually rose above control values. Angiotensin-converting enzyme inhibition by enalapril, begun at 8 weeks of age, was effective in completely normalizing the blood pressure, but did not totally prevent the extra mortality. Sprague- Dawley and Wistar rat strains developed equally severe hypertension after maternal protein deprivation, despite their different susceptibilities to nephrosclerosis with aging. In conclusion, maternal low-protein diet resulted in low birth weight and adult hypertension in the rat. Primary sodium retention and expanded extracellular volume may be critical factors during the development of the hypertension.

T cell CD3 receptor zeta (TCRζ)-chain expression in children with idiopathic nephrotic syndrome

Children with idiopathic nephrotic syndrome (INS) have an increased risk of developing life-threatening infections. Several studies have demonstrated functional abnormalities in the T lymphocytes of patients with nephrotic syndrome. Although T cells are activated in INS during relapse, as indicated by an increased expression of interleukin (IL)-2 receptor, these cells have a decreased ability to proliferate. The T-cell receptor (TCR) plays an important role in signal transduction and T cell activation, with the TCR-zeta (TCRζ) chain being a key element in early signaling. We measured the expression of the TCRζ chain in patients with INS (steroid resistant and steroid sensitive) during relapse and remission by flow cytometry and by PCR ELISA. The results showed a significant decrease in the expression of the TCRζ chain at both the protein and mRNA level in INS patients during relapse as compared with normal controls (p < 0.05). In contrast, when patients with INS achieved remission, the expression of TCRζ normalized and was similar to that expressed in normal controls. Therefore, a decreased expression of the TCRζ chain may explain the abnormal function of T cells in patients with INS, and it may also contribute to the increased risk for infections seen in these patients.

Effect of Maternal Low-Protein Diet on Blood Pressure and Longevity of the Offspring in the Rat

Effect of Maternal Low-Protein Diet on Blood Pressure and Longevity of the Offspring in the Rat

EXPRESSION OF RENAL COLLECTING DUCT AMILORIDE-SENSITIVE Na CHANNEL SUBUNIT GENES DURING MATURATION. |[dagger]| 2136

The rate-limiting step in Na transport by the renal cortical collecting duct is the apical amiloride-sensitive Na channel (ENaC), which is composed of three recently identified subunits (α, β, and γ). The immature CCD has a low rate of active Na transport and a very low Na-channel activity. To explore the mechanism, expression of the three ENaC subunit genes was studied in rat kidney at different developmental stages. Reverse transcription followed by polymerase chain reaction (rt-pcr) and agarose gel electrophoresis was used for specific mRNA detection. GAPDH mRNA, which did not show any age-related changes, was used as a positive control. All products were also partially sequenced to confirm their identity.

EXPRESSION OF |[alpha]| ISOFORMS OF THE Na-K-ATPase IN THE DEVELOPING KIDNEY.|[dagger]| 2130

The immature kidney has severe functional limitations in regulating sodium and potassium homeostasis. Both sodium reabsorption and potassium secretion in the kidney are mediated by the enzyme Na-K-ATPase. This enzyme is a heterodimer consisting of one α subunit (α1,α2, orα3) and one β (β1 or β2) subunit; the sodium affinity may differ between the α isoforms. Some organs, such as the heart, have been shown to exhibit a developmental switch from one isoform pattern to another during maturation. We investigated the possibility that a similar isoform switch occurs during renal maturation. Total RNA was isolated from fetal (20 days gestation, N=3) and adult (N=6) rabbit cortex. Specific mRNA species were detected by reverse transcription-polymerase chain reaction (RT-PCR), performed with primers specific for the three different α isoforms. Each isoform yielded a size specific product on agarose gel. GAPDH mRNA was measured simultaneously as a positive control. The polymerase chain reaction was performed in several animals from each group. All adult kidneys exhibited both α1 and α3 mRNA. In contrast, α1 mRNA was not detected in any of the fetal kidneys while α 3 mRNA was present in all of them. In conclusion, the Na-K-ATPase α isoforms appear to be developmentally regulated in the kidney. The different isoform pattern may explain some of the transport characteristics of the immature renal tubules.