Abstract P378: Dahl Salt-Sensitive Rats Exhibit Aberrant Renal Hemodynamic Responses to a High Salt Diet and Salt-Sensitive Hypertension as Compared to Consomic SS.BN1 Rats

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Altered renal vascular responses to a high salt diet have been proposed to contribute to salt-sensitive (SS) hypertension. The goals of this study were to assess: 1) SS hypertension and renal injury in Dahl SS vs. Brown-Norway (BN) and consomic SS.BN1 rats and 2) renal hemodynamics in conscious SS vs. SS.BN1 rats during consumption of a low and high salt diet. Systolic BP (24 hrs/day via telemetry), proteinuria and renal injury were assessed in 10 week old SS (n=9), BN (n=8) and SS.BN1 (n=8) rats during a 0.4% NaCl diet and for 3 weeks during a 4.0% NaCl diet. On a 0.4% NaCl diet, BP was different (P<0.05) among SS, BN and SS.BN1 rats (160±1 vs. 115±2 vs. 141±2 mmHg) while proteinuria was higher (P<0.05) in SS vs. BN and SS.BN1 rats (87±14 vs. 22±3 and 30±5 mg/day). A 4% NaCl diet exacerbated differences (P<0.05) in BP (188±3 vs. 122±2 vs. 150±1 mmHg) and proteinuria (259±29 vs. 29±5 vs. 68±15 mg/day) between SS vs. BN and SS.BN1 rats. Abundant uromodulin (UMOD) positive protein casts were only observed in SS rats. Interestingly, strikingly low levels of UMOD, located on chromosome 1, were found in the urine of SS vs. BN and SS.BN1 rats at baseline. Mean arterial BP (MAP, mmHg, via telemetry), renal vascular resistance (RVR, mmHg/ml/min) and renal blood flow (RBF, ml/min, via Transonic flow probe) were assessed in conscious 10 week old SS (n=5) vs. SS.BN1 (n=5) rats for 2-3 hrs/day over 3 days of 0.4% NaCl feeding and over days 3-7 of 4.0% NaCl feeding. While MAP was higher during a 0.4% NaCl diet in SS vs. SS.BN1 rats (137±3 vs. 121±3), interestingly, RVR was lower (16±2 vs. 20±2, P<0.05) and RBF higher (9±1 vs. 6±1, P<0.05) in SS vs. SS.BN1 rats. During 4.0% NaCl feeding, RVR decreased (17±2, P<0.05), RBF increased (8±1, P<0.05) and MAP remained unchanged (122±3) in SS.BN1 rats whereas RVR increased (19±3, P<0.05), RBF remained unchanged (8±1) and MAP increased (146±4, P<0.05) in SS rats. In conclusion, SS hypertension is abolished in SS.BN1 rats. Dahl SS rats exhibit an unexpected low RVR and high RBF when fed a 0.4% NaCl diet vs. SS.BN1 rats. Yet, SS rats display an impaired ability to lower RVR during a high salt diet as compared to SS.BN1 rats. These data warrant future investigations into the role that UMOD may play in altering renal hemodynamics, SS hypertension and CKD in Dahl SS rats.