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Abstract: SA-PO320

The Effects of Sacubitril and/or Valsartan on Renal Disease Progression in Salt-Sensitive Hypertension

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Domondon, Mark, Medical University of South Carolina, Charleston, South Carolina, United States
  • Polina, Iuliia, Medical University of South Carolina, Charleston, South Carolina, United States
  • Fomin, Mikhail, Medical University of South Carolina, Charleston, South Carolina, United States
  • Sudarikova, Anastasia, Medical University of South Carolina, Charleston, South Carolina, United States
  • Ilatovskaya, Daria, Medical University of South Carolina, Charleston, South Carolina, United States
Background

Available medications, such as diuretics and renin-angiotensin system (RAS) blockers, are often insufficient to control the blood pressure (BP) in the salt-sensitive (SS) hypertensive subjects. Abundant data support a pathogenic role for a low level of Atrial Natriuretic Peptide (ANP) in SS hypertension; ANP is known to promote salt excretion, vasodilation, and BP reduction. The goal of this project was to test if increasing the circulating ANP level using sacubitril in combination with a RAS blocker valsartan is beneficial for the alleviation of renal damage.

Methods

We performed chronic administration of sacubitril and/or valsartan at 75 ug/day to Dahl SS rats via an osmotic pump. All rats were fed a 0.4% NaCl (normal salt, NS) diet until 8 weeks of age, when they were challenged with a high salt (HS) 4% NaCl diet for 21 days. Vehicle, sacubitril (sacb), valsartan (val), or a 1:1 mix of both drugs (sacb/val) were administered together with HS diet; metabolic cage studies and GFR measurements were performed before the diet switch and at the end of the protocol.

Results

Upon a HS challenge, we observed renal hypertrophy reduction in the val group (p=0.047), and trend in the sac/val group (body weight was not affected). Urine flow was increased on HS diet compared to NS (p<0.01 for all groups), but not different between groups at the end of the protocol; we also observed a trend for lower water consumption in the sacb group. Upon a HS challenge, GFR was decreased in the control and elevated in the sacb/val and sacb groups; this increase was attenuated in the val treated animals. Interestingly, proteinuria was less pronounced in the sacb/val and val groups after 21 days on HS diet (vs control). In addition, we showed an increase in urinary KIM-1 in the control group, which was attenuated in the sacb/val and val animals.

Conclusion

Further mechanistic studies of the effects of sacubitril in the setting of SS hypertension are warranted in order to determine if pharmacological increase of circulating ANP level is a feasible therapeutic approach to interfere with the progression of the disease.

Funding

  • NIDDK Support