SAT-114 ABERRANT RENAL AND MESENTERIC HEMODYNAMIC RESPONSES TO A HIGH SALT DIET AND BLOOD PRESSURE SALT-SENSITIVITY ARE ABOLISHED IN CONSOMIC SS.BN1 vs. DAHL SS RATS

Abstract

The contribution of renal vs. systemic vascular dysfunction in the pathogenesis of salt-sensitive (SS) hypertension is a topic of considerable debate. The Dahl salt-sensitive (SS) rat is commonly used to investigate the genetic and pathophysiologic basis of SS hypertension. A consomic panel of rats in which individual chromosomes from the salt-resistant Brown-Norway (BN) rat are introgressed into the Dahl SS background have shown that genes on rat chromosome 1 play an important role in the pathogenesis SS hypertension. Here, we investigated renal injury as well as renal and mesenteric hemodynamics in conscious Dahl SS vs. consomic SS.BN1 rats fed low and high salt diets. Systolic blood pressure (BP, 24 hrs/day via telemetry), proteinuria and renal injury were assessed in 10-12 week old SS, BN and SS.BN1 rats fed a 0.4% or 4.0% NaCl diet for 3 weeks. Proteinuria and renal injury were also assessed in naïve 10-12 week vs. 5-6 month old SS, BN and SS.BN1 rats maintained on a 0.4% NaCl diet. BP (telemetry) and either renal blood flow (RBF, Transonic flow probe) or mesenteric blood flow (MBF, Transonic flow probe) were assessed (200 Hz, 2 hrs/day) in conscious 10-12 week old SS vs. SS.BN1 rats during 3 days of 0.4% NaCl feeding and during 5 days of 4.0% NaCl feeding. Finally, glomerular filtration rate (GFR) was assessed via creatinine clearance in 10-12 week old SS vs. SS.BN1 rats on a 0.4% NaCl diet and after 3 weeks of a 4.0% NaCl diet. SS hypertension was minimal and comparable in SS.BN1 and BN rats. In contrast, SS rats developed substantial increases in BP and proteinuria on a high salt diet. Glomerular and tubulointerstitial injury was prevalent in SS rats and correlated strongly with systolic BP. Significant renal injury and proteinuria was observed even in 10-12 week old SS, but not BN or SS.BN1, rats maintained on a 0.4% diet. Moreover, numerous abnormal tubules exhibiting enlarged hyperchromatic nuclei, non-isometric tubular vacuolization, loss of brush border and epithelial cell sloughing were observed in 10-12 week old SS rats. Frozen sections stained with H&E of kidneys from 10-12 week old SS rats showed protein plug formations within numerous tubule lumens. The magnitude of renal injury and proteinuria was substantially greater in 5-6 month old SS, but not BN or SS.BN1, rats fed a 0.4% NaCl diet as compared to respective 10-12 week old rats. When administered a 4.0% NaCl diet, SS.BN1 rats exhibited a significant decrease in renal vascular resistance (RVR) and increase in RBF but no change in mesenteric vascular resistance (MVR) or MBF. In contrast, RVR tended to increase and RBF decrease in SS rats fed a 4.0% high salt diet. Moreover, MVR significantly increased and MBF decreased in SS rats fed a high salt diet. GFR (normalized to body weight) tended to increase in SS.BN1 rats fed a high salt diet but no change was observed in SS rats. Introgression of chromosome 1 from the salt-resistant BN rat into the SS rat prevents SS hypertension. Such prevention is likely due, in large part, to a normal renal parenchyma and the ability of the renal vasculature to dilate and GFR to increase in response to a high salt diet. Moreover, the absence of aberrant increases in MVR during high salt feeding in SS.BN1 rats may further contribute to their resistance to SS hypertension.