Intestinal calcium transport, renal tubular calcium reabsorption, and plasma 1.25 (OH)2 vitamin D3 (calcitriol) levels have all been reported to be diminished in the spontaneously hypertensive rat (SHR) compared with its genetic control the Wistar Kyoto rat (WKY). In the present study, absorptive duodenal and renal tubular epithelia of 12- to 14-week-old male SHR and WKY were examined by electron microscopy to determine whether such disturbances could be related to structural abnormalities. Patchy loss of microvilli in both duodenal and proximal tubular epithelia was observed in the SHR, whereas brush border membrane was entirely normal in the WKY. Irregular spaces were observed between the basal aspects of SHR intestinal epithelial cells and their basement membrane. In addition, the average height of duodenal and renal microvilli was reduced in the SHR. Two specific markers of the brush border membrane, alkaline phosphatase and villin, as well as the cytoplasmic vitamin-D dependent calcium-binding proteins, CaBP9K and CaBP28K were determined. Duodenal alkaline phosphatase activity was reduced in the SHR, compared with the WKY: 0.145 +/- 0.002 vs. 0.186 +/- 0.002 IE/min.microns 3 x 10(3) brush border, mean +/- SEM, N = 10 pairs, P less than 0.001. However, duodenal villin expression was not different from that of the WKY. Duodenal CaBP9K and renal CaBP28K content was diminished in the SHR: 21.0 +/- 0.80 vs. 29.9 +/- 2.19 micrograms/mg protein, N = 6 pairs, P less than 0.01 for duodenum, and 4.47 +/- 0.39 vs. 7.67 +/- 0.54 micrograms/mg protein, N = 6 pairs, P less than 0.001 for kidney. These data showing structural and functional abnormalities of intestinal and kidney cells in the SHR appear to reflect a disorder of transporting epithelia which may be either intrinsic or related to reduced circulating calcitriol.

Recent reports have suggested that the action of calcitriol is much more rapid than previously thought. It is thus possible that some actions do not depend on de novo protein synthesis. A precise microdensitometric technique has been used to characterize the time course of the intestinal brush border alkaline phosphatase (AP) response of rat duodenal villi to the administration of calcitriol as AP activity has been shown to be dependent on the vitamin D status of the animal. The technique enables AP activity to be determined in situ without tissue disruption. After ip administration of 200 ng calcitriol to vitamin D-deficient male Wistar AF rats, a biphasic AP response was observed with an early peak within 1 h (0.068 +/- 0.011 vs. 0.101 +/- 0.003 integrated extinction (IE) min.micron 3 X 10(3), P less than 0.05) and a second at between 6 and 8 h (0.088 +/- 0.005 vs. 0.172 +/- 0.003 IE/min.micron 3 X 10(3), P less than 0.001). In a further experiment, the early response to calcitriol was reexamined with observations at 0, 10, 30, 45, and 60 min after administration of either calcitriol or vehicle (n = 5 pairs per time point). AP activity was significantly increased in the calcitriol group compared with the vehicle-treated group as early as 10 min after administration (0.132 +/- 0.003 vs. 0.151 +/- 0.005 IE/min.micron 3 X 10(3), P less than 0.02) and reached a peak 45 min after administration at which time AP activity was equal to that found in normal vitamin D-replete animals (0.193 +/- 0.003 vs. 0.192 +/- 0.002 IE/min.micron (3) X 10(3), P greater than 0.5). The speed of this response indicates it to be unlikely to depend on de novo protein synthesis.

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