Epithelial abnormalities in intestine and kidney of the spontaneously hypertensive rat.
A variety of perturbations of calcium metabolism are reported to occur in the spontaneously hypertensive rat (SHR) compared to its genetic control the Wistar-Kyoto rat (WKY), including significant dysfunction of calcium handling by the proximal renal tubule of the SHR, resulting in impaired active calcium transport in the gut and an apparent renal calcium leak. We explored the intestinal and renal epithelia of 12- to 14-week-old SHR and WKY using electron microscopy. Biochemical comparisons of these transport epithelia included measurements of three vitamin D dependent cellular proteins and one structural protein: alkaline phosphatase, intestinal CaBP9K, renal CaBP28K, and villin expression. Electron microscopy demonstrated a patchy loss in microvilli in the SHR, accounting for approximately 10 to 15% of the total microvillar surface. In the kidney, morphological abnormalities were observed only in the proximal renal tubule. Again, there was patchy loss of microvilli from the brush border membrane. In SHR duodenal alkaline phosphatase activity was significantly reduced compared to the WKY (0.145 +/- 0.002 v 0.186 +/- 0.002 integrated extinction/min/micron 3 X 10(3) brush border (P less than .001). Duodenal CaBP9K and renal CaBP28K were significantly reduced in SHR compared to WKY. There were no differences in villin expression. These data are consistent with the previously characterized disturbances of active calcium transport in the intestine and inappropriate renal calcium leak in the SHR. While a possible link between these disturbances and hypertension remains to be determined, this study provides supportive evidence for a primary disturbance in cell calcium handling and transporting epithelia in this form of genetic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Drüeke
T B
TB
INSERM Unité 90, Hôpital Necker, Paris, France.
Hennessen
U
U
Lucas
P A
PA
Nabarra
B
B
Ben Nasr
L
L
Thomasset
M
M
Lacour
B
B
Coudrier
E
E
McCarron
D A
DA
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism / Q000648:ultrastructure*; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D008840:Microfilament Proteins; C026615:villin; D000469:Alkaline Phosphatase; D002118:Calcium