Epithelial Abnormalities in Intestine and Kidney of the Spontaneously Hypertensive Rat

Abstract

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)

Proximal tubule Na transporter responses are the same during acute and chronic hypertension

“…Total alkaline phosphatase activity, measured in renal cortical membranes before fractionation, was 37% higher in young SHR compared with young SD (2.84 Ϯ 0.35 vs. 2.07 Ϯ 0.11 mol P i ⅐ mg protein Ϫ1 ⅐ h Ϫ1 P Ͻ 0.05), but was not different in adult SHR vs. SD (2.10 Ϯ 0.45 vs 2.05 Ϯ 0.45 mol P i ⅐ mg protein Ϫ1 ⅐ h Ϫ1 ), illustrating that the alkaline phosphatase activity in SHR fell significantly with age (P Ͻ 0.05). Likewise, other investigators have not seen a difference in alkaline phosphatase activity in adult hypertensive SHR vs. normotensive WKY (7,16). The pattern of a decrease in alkaline phosphatase activity with chronic hypertension is the same as the rapid decrease in activity during acute hypertension in the adult SD (Fig.…”

Differential visceral pain sensitivity and colonic morphology in four common laboratory rat strains

“…Nonetheless, they do display a patchy loss of intestinal microvilli and altered intestinal electrolyte transport (Lübcke & Barbezat, ; Drueke et al . ). In our studies, flattening of mucosal epithelial cells in this strain may be indicative of mild mucosal damage or cell restitution (Dignass et al .…”

“…Although SHRs are reported to have T-cell dysfunction, there is little evidence to show that SHRs are more susceptible to mucosal damage (Shichijo et al 2000;Blackler et al 2012). Nonetheless, they do display a patchy loss of intestinal microvilli and altered intestinal electrolyte transport (Lübcke & Barbezat, 1988;Drueke et al 1990). In our studies, flattening of mucosal epithelial cells in this strain may be indicative of mild mucosal damage or cell restitution (Dignass et al 1994).…”

“…Although SHRs have deficiencies in intestinal electrolyte transport (Lübcke & Barbezat, ; Drueke et al . ) and display a patchy loss of microvilli, they do not exhibit susceptibility to mucosal damage (Shichijo et al . ; Blackler et al .…”

“…Spontaneously hypertensive rats (SHRs) have frequently been used as comparators for WKY rats in studies examining hypertension, but in terms of anxiety they display fewer stress behaviours (Langen & Dost, 2011). Although SHRs have deficiencies in intestinal electrolyte transport (Lübcke & Barbezat, 1988;Drueke et al 1990) and display a patchy loss of microvilli, they do not exhibit susceptibility to mucosal damage (Shichijo et al 2000;Blackler et al 2012). The Sprague-Dawley (SD) rat was used as a control strain, because it has been used as a comparator for both maternally separated (MS) and WKY rats in previous studies carried out in our laboratory (O'Malley et al 2010a) and is considered to be a low-anxiety rat strain with low vulnerability to GI inflammation.…”