Envigo's Female Salt‐Sensitive Rapp Rats are now Spontaneously Hypertensive and have Higher Frequencies of CD4+, CD4+ CD25+ and CD4+ CD25+ FoxP3+ T cells compared to Normotensive Salt‐resistant Rapp Rats

Abstract

IntroductionWe and others have found female Rapp (Jr) salt‐sensitive (SS) rats recently purchased from Envigo, formerly Harlan (Hsd) and maintained on a low sodium diet are spontaneously hypertensive. To further investigate the role of T cells in the new phenotype of spontaneous hypertension (SH) observed in the Envigo's Rapp strain (SHSS/JrHsd), we compared the T cell profile in SHSS/JrHsd with that of the Rapp normotensive salt‐resistant rats (NSR/JrHsd).MethodsMean arterial pressure (MAP) was measured by radio‐telemetry in juvenile (j) 1 month old (mo) SHSS/JrHsd, and in young (y) adult 4 mo SHSS/JrHsd and NSR/JrHsd rats. Helper (CD4+) and cytotoxic (CD8+) T cells were assessed in the kidney by multicolor flow cytometry in 1 and 4 mo SHSS/JrHsd and NSR/JrHsd rats.ResultsRadio telemetry confirmed that 1 mo jSHSS/JrHsd rats had normal MAP [(mmHg): 100±1; n=13]. Blood pressure rapidly increased with age and was significantly higher in 4 mo ySHSS/JrHsd rats compared to age matched normotensive yNSR/JrHsd [(mmHg): yNSR/JrHsd, 103±2 vs. ySHSS/JrHsd, 160±11; p<0.007; n=3/group]. The frequencies of CD4+ (1.3 fold; p<0.0001), CD4+ CD25+ (1.5 fold; p=0.002) T cells and the CD4+/CD8+ ratio [(CD4+/CD8+): jNSR/JrHsd, 1.1±0.07 vs. jSHSS/JrHsd, 2.1±0.1; p<0.0001; n=8/group] were significantly higher in jSHSS/JrHsd compared to jNSR/JrHsd. The frequencies of CD4+ (1.4 fold; p<0.0001), CD4+CD25+ (2.1 fold; p<0.0001) T cells and the CD4+/CD8+ ratio [(CD4+/CD8+): yNSR/JrHsd, 1.6±0.07 vs. ySHSS/JrHsd, 5.6±0.6; p<0.0001; n=7–8/group] were even higher in ySHSS/JrHsd compared to yNSR/JrHsd. Moreover, the ySHSS/JrHsd rats had a higher frequency of CD4+CD25+ FoxP3+ T cells compared to the yNSR/JrHsd at 4 mo (2 fold; p=0.0009).ConclusionsFemale Rapp SS rats from Envigo (formerly Harlan; Hsd) are normotensive as juveniles but get spontaneous hypertension by the time they are 4 mo; they should more appropriately be referred to as SHSS/JrHsd Rapp rats. Our T cell findings support previous studies indicating CD4+ T cells and subtypes contribute to hypertension.Support or Funding InformationTL1‐TR001431 (AVP), UL1‐TR001409 (KS) and R01‐HL119380 (KS, HJ)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.