Thyroid hormone modulates rabbit proximal straight tubule paracellular permeability.
Proximal straight tubules (PST) from both neonatal and hypothyroid adult rabbits have a lower rate of passive volume absorption when perfused with a high-chloride solution simulating late proximal tubular fluid than adult rabbit PST. We hypothesized that the maturational increase in serum thyroid hormone levels mediates the developmental changes in PST paracellular permeability. Neonatal tubules had lower chloride permeability, higher transepithelial resistance, but comparable mannitol permeability compared with adult PST. The present in vitro microperfusion study directly examined whether thyroid hormone affects passive solute flux and whether thyroid hormone could explain the developmental changes in PST paracellular permeability. Passive chloride transport was 62.1 +/- 4.5, 23.1 +/- 7.7, and 111.6 +/- 5.6 pmol.mm(-1).min(-1) in PST from euthyroid, hypothyroid, and hypothyroid animals that received thyroid treatment, respectively (control different from hypothyroid and thyroid treatment at P < 0.05). This was due to a thyroid hormone-mediated change in chloride permeability (P(Cl)). Mannitol permeability was 3.65 + 1.03, -0.19 + 0.72, and 3.60 + 1.12 x 10(-6) cm/s in PST from euthyroid animals, hypothyroid animals, and hypothyroid rabbits that received thyroid replacement, respectively (P < 0.05 hypothyroid vs. euthyroid and thyroid replacement). We demonstrate that PST from hypothyroid animals have a higher passive P(Na)/P(Cl) and P(HCO3)/P(Cl) than euthyroid controls. Finally, we examined whether these changes in permeability were paralleled by a change in PST paracellular resistance. Resistance was measured by current injection and cable analysis. The resistance in PST from hypothyroid rabbits was 6.3 +/- 0.8 Omega.cm(2), which was not different from control of 4.8 +/- 0.7 Omega.cm(2), or 7.0 +/- 0.7 Omega.cm(2) in hypothyroid animals that received thyroid replacement. Therefore, the maturational increase in thyroid hormone levels does not fully explain the developmental changes in the paracellular pathway.
Baum
Michel
M
Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9063, USA. michel.baum@utsouthwestern.edu
Quigley
Raymond
R
D000818:Animals; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000378:metabolism; D046508:Culture Techniques; D017097:Electric Impedance; D004847:Epithelial Cells / Q000502:physiology; D007037:Hypothyroidism / Q000209:etiology; D017136:Ion Transport; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D008353:Mannitol / Q000378:metabolism; D011817:Rabbits; D013963:Thyroid Hormones / Q000502:physiology*
D002712:Chlorides; D013963:Thyroid Hormones; D008353:Mannitol