High Salt Diet Induces a Rapid Increase in Blood Pressure and Mortality in the Ren −/− Dahl SS Rats

Renin‐angiotensin system (RAS) is an important regulator of fluid balance and blood pressure (BP), demonstrated by the widely employed use of angiotensin receptor and/or ACE inhibitors to control hypertension in humans. Here we used the renin knockout (Ren −/− ) rats generated on the Dahl Salt‐Sensitive (SS) rat background to address the question of BP development in the absence of renin. Ren −/− rats exhibit polyuria, lower body weight and mean arterial pressure (MAP) (65.9 ± 2.1 in Ren −/− rats vs 121.9 ± 1.9 mmHg in the wild type (WT) littermates). Baseline glomerular filtration rate (GFR) is also lower in the Ren −/− rats compared to WT littermates (0.54 ± 0.04 vs 0.19 ± 0.03 mL/min/100 g of body weight). To test the role of renin in the BP regulation during the development of salt‐induced hypertension, Ren −/− rats and their WT littermates were kept on 0.4% NaCl diet since weaning (normal salt, NS), and then challenged with sodium deficient (SD, 0.01% NaCl) or high salt (HS, 4% NaCl) diets. BP was recorded via telemetry, kidney function was evaluated by GFR measurements, and diuresis was assessed in metabolic cages. After 10 days of a HS dietary challenge, 24 hr urinary output, sodium excretion, GFR and BP were elevated in the WT littermates, as expected. After a HS diet was introduced to Ren −/− rats there was a very rapid raise in MAP in the Ren −/− rats (ΔMAP was 60.4 ± 7.1 mmHg over a 5‐day period, compared to 5.0 ± 0.4 mmHg in the WT littermates). In the Ren −/− group, HS diet caused mortality. Neither of Ren −/− rats survived more than 13 days (8 days if animals were instrumented with a telemetry device), which was not observed in the WT littermates. Additionally, Ren −/− rats fed a HS diet had an increase in diuresis and sodium excretion during the first 2–4 days, which was blunted before the terminal point. Following an initial increase, a dramatic decline in GFR was also observed in these rats. Furthermore, before the endpoint there was a spike in plasma sodium level (up to 180 mMol/L) in the Ren −/− animals challenged with a HS diet. SD diet did not significantly affect MAP or survival in either group within 12 days of the observations. All SD diet fed animals showed reduced urinary output compared to rats fed a NS diet; however, no difference was found in electrolyte excretion between groups fed a SD diet. GFR was not affected in either group fed a SD chow. Therefore, BP in the Ren −/− rat increases in response to a HS diet, which suggests an involvement of the non‐renin components in this mechanism. Furthermore, we demonstrated that Ren −/− animals are able maintain homeostasis when challenged a SD diet. These data open new avenues to understanding the role of RAS in SS hypertension. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .