Ultrastructural and functional abnormalities of intestinal and renal epithelium in the SHR

Abstract

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.

Decreased Calcium Pump Activity in Duodenal Epithelial Cells from Spontaneously Hypertensive Rats

“…A patchy loss of microvilli detected by Drueke et al (22) was not detected on the SHR cell in the present work. This discrepancy might be due to the difference of the method.…”

Chronic Cigarette Smoke Causes Oxidative Damage and Apoptosis to Retinal Pigmented Epithelial Cells in Mice

“…The choriocapillaris endothelium appeared healthy with fenestrations. We chose RPE basolateral infoldings and cytoplasmic vacuoles as indicators of RPE cell degeneration because loss of basal infoldings is a marker of epithelial injury [28]–[30] and cytoplasmic vacuoles have been identified in RPE that overlie drusen deposits [13]. Figure 2 also shows an 8 mo old mouse that has been exposed to chronic cigarette smoke exhibiting ultrastructural injury to the RPE-Bruch membrane.…”

“…The 8-OHdG immunohistochemical experiments indicate that despite a significant anti-oxidant defense system, the RPE developed oxidative DNA damage in mice exposed to cigarette smoke. The most obvious ultrastructural sign of injury to the RPE was enlargement and loss of basolateral infoldings, which is an established marker of epithelial cell injury from a number of etiologies including oxidative stress [28]–[30]. We used vacuole formation as a second sign of RPE change because it is known to occur in RPE cells overlying drusen deposits [13].…”

Magnesium Uptake by Intestinal Brush-Border Membranes of Spontaneously Hypertensive Rats

“…On the other hand, structural abnormalities have been recorded in duodenal microvilli of SHR (20), and sound modifications of duodenal and jejunal brushborder-bound enzymes have been reported (14, 15,2 1). These alterations could also participate in Ca2+ and Mg" malabsorption.…”