Recent reports have shown that low birth weight infants have a higher incidence of adult hypertension. These observations have stimulated a number of studies designed to evaluate the mechanisms of this phenomenon. In this study, fetal growth retardation was induced by treating pregnant rats with dexamethasone. After birth, pups whose mothers were treated with dexamethasone had a lower body and kidney weight and a lower number of glomeruli than control pups. Immunohistochemistry on treated kidneys demonstrated a marked reduction in the number of cells undergoing mitosis in the cortical nephrogenic zone. In the treated group, body and kidney weight normalized by 60 d of age, but blood pressure was significantly higher compared with controls (130+/-4 versus 107+/-1 mm Hg). In addition, GFR was significantly lower, albuminuria was higher, urinary sodium excretion rate and fractional sodium excretion were lower, and sodium tissue content was higher. In contrast, when pregnant rats were treated with a natural glucocorticoid (hydrocortisone) which is metabolized by the placenta, fetal development and adult blood pressure were normal. In conclusion, we found that high levels of maternal glucocorticoids impair renal development and lead to arterial hypertension in offspring. Even though renal mass eventually normalizes, glomerular damage as well as sodium retention occur and these factors may contribute to the development of hypertension.

The coupling between the Na+/glucose cotransporter and Na(+)-K(+)-ATPase (NKA) described for epithelial cells (1) prompted us to study in rats with streptozocin-induced diabetes the effect of increased tubular glucose load on tubular Na+ reabsorption, NKA-dependent O2 consumption (QO2), and NKA activity. Filtered glucose is mainly reabsorbed in the proximal tubuli via the phlorizin-sensitive Na+/glucose cotransporter. In this study, the diabetic rats had a significantly higher renal blood flow (RBF), glomerular filtration rate (GFR), and Na+ reabsorption than the control rats. Total renal QO2 as well as QO2 in cortical tissue, which consists mainly of proximal tubular cells, was significantly higher in diabetic than in control rats. The increase in tissue QO2 was entirely caused by increased NKA-dependent QO2. NKA activity, measured as rate of ATP hydrolysis, was increased in cortical tubular but not glomerular tissue from diabetic rats. Phlorizin treatment abolished the increase in NKA activity, Na+ reabsorption, and QO2, as well as the increase in RBF and GFR in diabetic rats. We conclude that diabetes is associated with increased renal O2 metabolism secondary to the increase in coupled Na+ reabsorption via the Na+/glucose cotransporter and NKA. The increased oxygen consumption might contribute to the hyperperfusion and hyperfiltration in the diabetic kidney.

Dopamine is a natriuretic hormone that acts by inhibiting tubular Na + JC + -ATPase activity by activation of the dopamine-1 receptor (the thick ascending limb [TAL] of Henle) or by a synergistic effect of dopamine-1 and dopamine-2 receptors (the proximal tubule). The dopamine-1 receptor is coupled to adenylate cyclase. In this article we show that prehypertensive Dahl salt-sensitive (DS) rats have a blunted natriuretic response to dopamine determined during euvolemk conditions compared with Dahl salt-resistant (DR) rats. Furthermore, we have examined the renal tubular effects of dopamine in DS and DR rats. Basal Na 5 Activation of the DA-1 receptor is in both cases associated with adenylate cyclase activation.Several lines of evidence suggest that an aberrant renal dopaminergic system may be a factor in the pathogenesis of salt-sensitive hypertension.6 " 8 This has prompted us to examine the renal effects of dopamine in the Dahl salt-sensitive (DS) rat. The DS rat is extremely sensitive to the blood pressure elevation effect of a high salt diet 9 and exhibits impaired intrinsic natriuretic capacity.1011 Its control strain is the Dahl salt-resistant (DR) rat, which remains normotensive even during long periods of high salt intake.We show that Na + ,K + -ATPase activity in the PT and TAL segments from DS rats are, in contrast to DR rats, Received March 18, 1992; accepted in revised form January 13, 1993. not responsive to dopamine and the DA-1 agonist fenoldopam. We also show that DS rats have an attenuated natriuretic response to dopamine. In addition, our studies on the effects of dopamine on renal cyclic adenosine monophosphate (cAMP) levels and the effects of cAMP on tubular Na + ,K + -ATPase activity add evidence to the hypothesis, originally suggested by Felder et al,[12][13] that the coupling of the DA-1 receptor to adenylate cyclase may be defective in genetic hypertension. Methods AnimalsStudies were performed on male prehypertensive DS (SS/Jr) and DR (SR/Jr) rats aged 7-8 weeks and weighing 160-240 g. These rats were purchased from M0llegaards Breeding Center, Ejby, Denmark. The rats receiving a normal salt diet were fed a standard rat chow (R3, Ewos, Sodertalje, Sweden) that contains 0.7% NaCl and received tap water ad libitum.Rats were anesthetized with Inactin-Byk (Byk-Gulden, Konstanz, FRG) (80 mg/kg body wt i.p.). Mean arterial pressure was recorded via one carotid artery. Inactin-Byk anesthesia does not influence mean arterial pressure, as shown previously.14 Mean arterial pressure values were similar in DS and DR rats on a normal salt diet (116±3 versus 110±2 mmHg). Preparation of TubulesKidney perfusion and tubule microdissection were performed as described.15 After a midline incision, the left kidney was exposed and perfused with the following modified Hanks' solution (mM): N a d 137, KQ 5, MgSO<