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.
Highlights
The renin angiotensin system (RAS) is an important modulator of blood pressure (BP) and sodium homeostasis
No differences were observed in 24 hour systolic or diastolic BP between floxed and collecting duct (CD) renin knock out (KO) mice fed a normal Na+ diet (Fig 1)
No differences were observed in heart rate between floxed and CD renin KO mice prior to and doi:10.1371/journal.pone.0159872.g001
Summary
The renin angiotensin system (RAS) is an important modulator of blood pressure (BP) and sodium homeostasis. Collecting Duct Renin and DOCA-Salt enzyme are expressed in the renal tubule leading to luminal Ang-II synthesis [5,6,7,8], which in turn can modulate electrolyte and water reabsorption and BP. Medullary renin mRNA and protein levels are increased in 2-kidney, 1-clip Goldblatt hypertensive rats [11] and transgenic rats with inducible extra-renal mouse renin gene (Ren2) expression [12]. CD renin fluorescence by multi-photon confocal microscopy and medullary renin activity is increased in streptozotocin-induced diabetic rats [13]. These studies suggest that CD renin may be important in pathological states such as hypertension and diabetes. In contrast to JGA renin, renin synthesis in the CD is up regulated by systemic Ang-II [4]
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