Collecting Duct Renin Does Not Mediate DOCA-Salt Hypertension or Renal Injury

Abstract

Collecting duct (CD)-derived renin is involved in the hypertensive response to chronic angiotensin-II (Ang-II) administration. However, whether CD renin is involved in Ang-II independent hypertension is currently unknown. To begin to examine this, 12 week old male and female CD-specific renin knock out (KO) mice and their littermate controls were subjected to uni-nephrectomy followed by 2 weeks of deoxycorticosterone acetate (DOCA) infusion combined with a high salt diet. Radiotelemetric blood pressure (BP) was similar between KO and control mice at baseline; BP increased in both groups to a similar degree throughout the 2 weeks of DOCA-salt treatment. Urinary albumin excretion and plasma blood urea nitrogen were comparable between the two groups after DOCA-salt treatment. Fibrosis as assessed by Masson’s Trichrome stain/Sirius Red stain and collagen-1 mRNA expression was similar between control and KO mice. Compared to baseline, DOCA-salt treatment decreased plasma renin concentration (PRC), urinary renin excretion and medullary renin mRNA expression in both floxed and CD renin KO mice with no detectable differences between the two groups. Further, in primary culture of rat inner medullary CD, aldosterone treatment did not change renin activity or total renin content. Taken together, these data suggest that CD derived renin does not play a role in DOCA-salt hypertension.

Ameliorative effect of phosphodiesterase 4 and 5 inhibitors in deoxycorticosterone acetate‐salt hypertensive uni‐nephrectomized KKA y mice

“…Therefore, it was unknown whether mice treated with only DOCA‐salt show renal fibrosis. Similar experimental designs have been reported by other groups 29‐31 . We also performed UNx in DOCA‐salt‐treated KKA y mice but did not include only a DOCA‐salt‐treated group without UNx.…”

Inappropriate activity of local renin-angiotensin-aldosterone system during high salt intake: impact on the cardio-renal axis

“… 24 However, in a DOCA salt hypertension model, collecting duct renin is not essential to the development of hypertension and renal injury. 25 …”

DOCA-Salt Hypertension: an Update

“…Song et al performed a study in 2016 looking at the kidneys’ (specifically the collecting ducts) role in the low-renin, DOCA-salt hypertension model. When renin was selectively removed from the collecting ducts, there was no amelioration of hypertension, and no improvement of renal injury, observed in animals that went through the DOCA-salt protocol, opposite to what was observed in the Ang-II infusion model [72]. This indicates that while RAS components of the kidneys could play a role in certain types of hypertension (e.g., high-renin forms), the intrarenal RAS may not be involved in the pathology of low-renin forms of hypertension.…”