Viscoelastic properties of tubule basement membranes in experimental renal cystic disease.
Hereditary and acquired renal cysts develop from tubule segments that enlarge progressively. We measured the deformability of basement membranes surrounding individual normal tubules and cysts to determine if cysts might develop by simple extension of abnormally-deformable basement membrane in response to normal or increased transtubule hydrostatic pressures. Deformability (cm/dyne) was measured in individual tubules and cysts in vitro by a micropipet aspiration technique that related negative pressures within the pipet to the distance the tubule or cyst wall was aspirated into the pipet. Viscoelastic creep was determined from the time-dependent effect of pipet aspiration on membrane deformation. Proximal and collecting tubules, glomerular capsules and cysts were microdissected from controls and animals with acquired (Diphenylthiazole [rats]. Nordihydroguaiaretic acid [rats]), hereditary (C57 BL/6J [cpk/cpk] mice) and spontaneous (CFWw mice) renal cystic diseases. The major resistance to deformation was localized to the basement membrane since collagenase destroyed the elasticity of tubule and cyst walls. Tubule basement membranes adjacent to cysts appeared abnormal by electron microscopy in the animals fed DPT, but measurements of deformability and viscoelastic creep showed no differences between normal and cystic tubules in any animal model. Deformability values of cysts (7.7 +/- 1.1, 10.9 +/- 1.1, 11.2 +/- 0.6, 9.4 +/- 0.8 X 10(-3) cm/dyne in DPT, NDGA, C57 BL/6J and CFWw, respectively) are consistent with the interpretation that high transtubule pressures ranging from 39 to 134 cm H2O would be required if cysts form by simple stretching of the basement membrane secondary to a transepithelial hydrostatic pressure-gradient. Since in vivo measurements of hydrostatic pressures across cyst walls are not high enough we conclude that cysts do not enlarge due to increased deformability of tubule basement membranes.
Grantham
J J
JJ
Department of Medicine, Kansas University Medical Center, Kansas City.
Donoso
V S
VS
Evan
A P
AP
Carone
F A
FA
Gardner
K D
KD
D000818:Animals; D001485:Basement Membrane / Q000503:physiopathology / Q000648:ultrastructure; D004548:Elasticity; D052177:Kidney Diseases, Cystic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D007684:Kidney Tubules / Q000503:physiopathology* / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D014783:Viscosity