Corn Bedding Mediates Protection from the Dahl Salt‐Sensitive Hypertensive and Renal Damage Phenotype

Abstract

The Dahl Salt‐Sensitive (SS) rat is a well‐established translational model of human salt sensitive hypertension. When challenged with a high salt (4.0% NaCl) diet, Dahl SS develop an increase in mean arterial pressure (MAP) and renal damage, as assessed by an increase in albumin excretion and infiltration of immune cells in the kidneys. Our colony of Dahl SS recently moved to a new animal facility, and we observed that the SS rats challenged on a high salt diet showed an attenuation of the high salt‐induced increase in MAP and albumin excretion. Upon further investigation, differences in the animal bedding were noted between the locations. In the present study, the salt‐sensitive disease phenotype was examined in age‐matched, genetically‐identical male Dahl SS rats fed the same diets (AIN‐76A with 0.4% or 4.0% NaCl) maintained on either an aspen‐based wood bedding or a corn‐cob based bedding. Based upon the known protective effects of a plant‐based diet and observations that the rats were eating the corn‐cob bedding, we hypothesized that the change in bedding from wood to corn was providing a protective phenotype to the SS rats. We tested this hypothesis by comparing the disease phenotypes in Dahl SS maintained on the corn‐cob or wood bedding from birth until the end of the study. SS rats were instrumented at 7 weeks of age with radiotelemeters for continuous blood pressure monitoring and were allowed about a week to recover. While the rats were maintained on a low salt (0.4% NaCl) diet, there were no significant differences in MAP (123.2±1.1 vs 126.8±0.8 mmHg, n=13, 16) or albumin excretion rate (7.5±1.8 vs 18.8±3.5 mg/day, n=10, 17) in Dahl SS maintained on the corn‐cob vs the wood bedding, respectively. While MAP and albumin excretion significantly increased in all Dahl SS following a 21‐day high salt challenge, there was significantly reduced albumin excretion in the corn‐cob bedding rats (128±27 mg/day, n=10) when compared to the wood bedding rats (332±50 mg/day, n=17, p˂0.005). The SS rats maintained on the corn‐cob bedding also had significantly attenuated MAP at the end of the 21 day challenge when compared to the rats on the wood bedding (corn‐cob bedding: 141.1±4.2 mmHg vs wood bedding: 159.5±3.6 mmHg, p˂0.0001, n=12, 16 respectively). This was further characterized with a significant reduction in CD45+ leukocytes infiltrating in the SS rat kidneys on corn‐cob bedding by ~48% (p<0.003). That occurred by a significant reduction observed in the CD11b/c+ macrophages/monocytes by ~49% (p<0.003) and in CD45R+ B‐cells by ~64% (p<0.004). There was no difference between the body weights of the rats between the different beddings (corn‐cob bedding: 336±6 g vs wood bedding: 339±5 g, n=13, 17) respectively but kidney weight was a significantly reduced by ~17% (p<0.0001) in corn‐cob bedding compared to the SS rats on the wood bedding. This attenuated phenotype was also mirrored in female Dahl SS rats when maintained on the corn‐cob bedding compared to age‐matched females on the wood bedding. These data suggest that the change in bedding from wood to corn had a significant protective effect in the Dahl SS rat. Further work will need to be performed to determine the exact cause in the reduction of the salt‐sensitive phenotype when on a corn‐cob bedding. These data highlight the importance of controlling all environmental parameters in experimental work, and to consider environmental effects that may influence other disease phenotypes.