An accumulation of the connective tissue component, hyaluronan (HA), is known to occur in both syngeneic and allogeneic kidney grafts during the early postoperative period. The presence of HA in the interstitial tissue of the grafts is paralleled by an increased water content, suggesting a role for HA in the development of the transplantation edema. In the present work, the kidney content and distribution of HA was studied in a model of warm renal ischemia in the rat to investigate whether renal ischemia is associated with HA accumulation. Seventy-two hours after a period of warm renal ischemia (30 or 60 min) significantly higher amounts of HA were observed in the left kidney that had been exposed to ischemia, than in the right, healthy kidney. The most pronounced increase was found to occur in the cortex (20 to 40 times), a structure where there normally is almost no presence of HA. In addition, there was a correlation between the relative water content of the kidney and the amount of HA possible to extract from the tissue. The renal accumulation of HA and water was prevented by daily intravenous administration of hyaluronidase. We conclude that renal ischemia induces an accumulation of HA that may increase the risk for the development of interstitial edema, a situation that may be circumvented by hyaluronidase treatment.
SUMMARYThe immunomodulatory properties of the vitamin D analogue MC 1288 (20-epi-1a,25-dihydroxycholecalciferol) were investigated in CIA in rats. The analogue was administered systemically at three different time points; (i) for 10 consecutive days before collagen (CII) immunization; (ii) for 10 consecutive days after CII immunization; or (iii) for 7 consecutive days from disease onset. Treatment initiated either 10 days before CII immunization or at the day of collagen immunization effectively suppressed the development of arthritis. Treatment initiated at the day of the onset of arthritis reduced the severity of joint inflammation. Significantly, doses which did not induce hypercalcaemia decreased the incidence and severity of arthritis. In vivo treatment with the 20-epi analogue of 1a,25-dihydroxycholecalciferol diminished the serum levels of antibodies to rat CII. Similarly, mitogen-induced proliferation of lymph node cells from rat CII-immunized animals was reduced. The experiments demonstrate that the vitamin D analogue MC 1288 has the ability to prevent, and furthermore to suppress, already established CIA by its immunomodulatory properties without inducing hypercalcaemia.
IR injury depresses parameters of renal function, which coincides with an elevated cortical HA content and Has 2 expression. The enhanced Has 2 expression indicates that the cortical HA accumulation is primarily dependent on increased HA synthesis and not impaired degradation/elimination. The water binding and pro-inflammatory properties of HA may contribute to renal dysfunction after IR.
Our previous studies in rats have suggested a role for renomedullary hyaluronan (HA) in water homeostasis. The gerbil is known for its unique ability to conserve water. In the present study renal papillary and intestinal HA were compared between groups of anaesthetized gerbils and rats before and after up to 6 h of i.v. water loading. Baseline papillary HA in gerbils was only 37 % of that in the rat. Water loading in rats increased the papillary HA content. Elevation was maximal (+27 %, P < 0.05) after 2 h of water loading and then declined to control levels after 6 h of water loading (+3 %, n.s.). In contrast, the gerbil responded with a decreased papillary HA content during water loading. The depression was maximal after 2 h (‐49 %, P < 0.05) and was still 41 % below the control values after 6 h (P < 0.05). The urine flow rate increased rapidly in the rat and its maximum, 21 times above the control level (P < 0.05), occurred at the HA peak, i.e. after 2 h of water loading while in the gerbil, the urine flow rate increased slowly and slightly and was only six times above control values after 6 h of water loading (P < 0.05). The HA content along the intestine was similar in the two species: lowest in the duodenum and jejunum and highest in the distal colon. To conclude, in the rat, the elevation of papillary interstitial HA during acute water loading would counteract water reabsorption by changing the physico‐chemical characteristics of the interstitial matrix favouring rapid water diuresis. This would work as a complement to the powerful regulation by ADH. The gerbil has a diametrically different regulation of papillary HA turnover during water loading. The decreased papillary HA level during water loading and the slow and small diuretic response may represent a genetic difference in adaptation to enhance the ability to conserve water in an arid environment.
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