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We have recently demonstrated that the rates of both active and passive proximal straight tubule (PST) NaCl transport in neonatal rabbits were less than in adults. In this segment NaCl entry across the apical membrane is via parallel Na + /H + and Cl − /OH − exchangers, which increases in activity with maturation. The present in vitro microperfusion study examined whether thyroid hormone plays a role in the maturational increase in PST NaCl transport. Neonatal and adult PST were perfused with a high-chloride-low bicarbonate solution without organic solutes, simulating late proximal tubule fluid. Thyroid hormone-treated neonates had a higher rate of PST total and passive NaCl transport. In 8-wk-old animals that were hypothyroid since birth, the maturational increase in total and passive NaCl transport was prevented. Thyroid treatment for 4 days in hypothyroid 8-wk-old rabbits increased the rate of both total and passive NaCl transport. The maturational increases in both Na + /H + and Cl − /OH − exchange activities were blunted in 8-wk-old hypothyroid animals and increased to control levels with thyroid treatment. This study demonstrates that thyroid hormone is a factor responsible for the maturational increase in both active and passive PST NaCl transport.Keywords sodium/hydrogen antiporter; chloride/base exchanger; kidney development; passive transportThe Proximal Tubule Reabsorbs ~60% of the filtered NaCl. The preferential reabsorption of organic solutes and bicarbonate by the early proximal tubule leaves the luminal fluid with a higher chloride and lower bicarbonate concentration than the peritubular plasma (19,24). In the proximal tubule approximately one-half of NaCl transport is passive and paracellular (4,25). The parallel operation of the apical membrane Na + /H + antiporter and Cl − /base exchangers mediate NaCl entry into the proximal tubule cell (1,18,25 We have recently examined the postnatal developmental changes in proximal straight tubule (PST) NaCl transport (25). In rabbit PST perfused with a high chloride-low bicarbonate solution simulating late proximal tubular fluid and bathed in a serum-like albumin solution, the rate of volume absorption, a reflection of both active and passive NaCl transport, was over twofold higher in the adult than neonatal segment (25). NaCl transport was inhibited by 50% by bath ouabain in adult tubules and totally inhibited in the neonatal segment. Thus the rates of active and passive NaCl transport were higher in the adult tubule than were those in the neonate (25).In the rabbit PST there was a fivefold increase in the Na + /H + antiporter activity during postnatal development (25). Cl − /base exchange in neonatal and adult PST was not affected by cyanide and acetazolamide, CO 2 and bicarbonate, or the addition of formate, consistent with Cl − /OH − exchange (18, 25). There was a sixfold maturational increase in apical membrane PST Cl − /OH − exchange activity (25).The factors that produce the profound postnatal changes in active and passive proximal tubular t...

The present in vitro microperfusion study compared the mechanism and rates of NaCl transport in neonatal and adult rabbit proximal straight tubules. In proximal straight tubules perfused with a late proximal tubular fluid and bathed in a serumlike albumin solution, the rate of volume absorption (J V ) was 0.54 ± 0.10 and 0.12 ± 0.05 nl·mm −1 ·min −1 in adults and neonates, respectively (P < 0.05). With the addition of 10 −5 M bath ouabain, J V decreased to 0.27 ± 0.07 and −0.03 ± 0.04 nl·mm −1 ·min −1 in adult and neonatal tubules, respectively (P < 0.05), consistent with lower rates of active and passive NaCl transport in the neonatal proximal straight tubule. The effect of luminal sodium and chloride removal on intracellular pH was used to assess the relative rates of Na + /H + and Cl − /base exchange. The rates of Na + /H + and Cl − /base exchange were approximately fivefold less in neonatal proximal straight tubules than adult tubules. In both neonatal and adult proximal straight tubules, the rate of Cl − /base exchange was not affected by formate, bicarbonate, or cyanide and acetazolamide, consistent with Cl − /OH − exchange. These data demonstrate an increase in proximal straight tubule NaCl transport during postnatal renal development.Keywords renal development; intracellular pH; sodium chloride transport; sodium/proton antiporter The proximal convoluted tubule preferentially reabsorbs organic solutes and bicarbonate, leaving the luminal fluid with a higher chloride concentration than that in the peritubular plasma (15,16). This chloride concentration gradient provides a driving force for passive chloride diffusion across the para-cellular pathway. In addition to passive chloride transport, there is active electroneutral transcellular NaCl transport by the proximal tubule (2, 7). In the adult rabbit proximal convoluted tubules perfused with a late proximal tubular fluid, approximately two-thirds of NaCl transport is active and one-third is passive (7).The parallel operation of the Na + /H + antiporter and Cl − /base exchange is thought to mediate net NaCl transport across the apical membrane of the proximal tubule (3, 5). There is (11,12). Thus the parallel operation of Cl − /formate exchange and the Na + /H + antiporter with formic acid recycling could mediate net NaCl transport (3,12). Indeed, formate has been shown to stimulate NaCl transport when added to the apical and bathing solutions of proximal convoluted and straight tubules perfused in vivo and in vitro (14,18,19,23,24).The rate of bicarbonate transport by the neonatal proximal tubule and apical membrane Na + /H + antiporter activity are less in the neonatal proximal tubule than in the adult (4,6,20). Nonetheless, the luminal concentration of bicarbonate decreases along the length of the proximal tubule (20). The mechanism of NaCl transport in the neonate is unknown. The present in vitro microperfusion study examined the relative rates of active and passive NaCl transport in neonatal and adult proximal straight tubules. We also examine...

Thirty male pesticide formulators exposed to the dust and liquid formulation of endosulfan, quinalphos, chlorpyriphos, monocrotophos, lindane, parathion, phorate, and fenvalerate and 20 comparable control subjects from the same area of study were examined for the evaluation of thyroid function tests. The level of TSH was elevated (about 28%) in pesticide formulators as compared to a control group, but the increase was statistically insignificant. Based on the individual TSH measurement, 3 of 30 formulators had isolated elevated levels of TSH and seem to have acquired sub-clinical hypothyroidism; five had TSH values slightly elevated to the upper boarder line (4.03,uIU/ml); and the majority of formulators (N= 22) had TSH values in the normal range varying from 1.29 to 3.9 pIU/ml. Total T3 was suppressed significantly (P <0.01) in formulators, while marginal decrease (about 7%) was noticed in T4 level. This studyindicatedthyroidfunctionimpairmentinfewpesticide formulators.