Blood pressure responses to dietary salt in renin-deficient Dahl salt-sensitive rats.

The renin-angiotensin-aldosterone system (RAAS) is essential in controlling fluid balance and blood pressure. In salt-sensitive (SS) hypertension, circulating RAAS is overactive, and the renin response to changes in sodium intake is bidirectionally blunted. Here, we used wild-type Dahl SS rats and renin knockout rats on the Dahl SS background (SSren-/-) to understand the role of renin in blood pressure regulation under salt-deficient (SD; 0.01% NaCl) and high-salt (HS; 4% NaCl) diets. We hypothesized that, compared with SSWT rats, SSren-/- rats would have lower blood pressure on the SD diet due to underdeveloped medulla and would return to normal blood pressure on the HS diet. First, we examined circulating RAAS after 10 days of SD and HS diets in SSWT rats. A 10-day SD diet robustly activated all parts of the circulating RAAS in Dahl SS rats, whereas a 10-day HS diet significantly decreased the aldosterone-to-Ang II ratio. In addition, we measured mean arterial blood pressure, glomerular filtration rate, urine output, and blood and urine electrolyte levels in SSren-/- rats and SSWT rats (littermates) under normal salt (NS; 0.4% NaCl) and after 10 days of SD or HS diets. SD feeding significantly reduced the blood pressure, plasma Na+, and Cl- of SSren-/- rats. HS diet caused a rapid rise in blood pressure, with 100% mortality in SSren-/- rats. In summary, these findings demonstrate that loss of renin impairs adaptive responses to dietary salt, and proper RAAS function is vital for maintaining blood pressure in salt-sensitive hypertension.NEW & NOTEWORTHY A 10-day high-salt diet caused a rapid increase in blood pressure and 100% mortality in renin-deficient Dahl salt-sensitive rats, demonstrating that intact renin-angiotensin-aldosterone system (RAAS) signaling is essential for blood pressure regulation in salt-sensitive hypertension.