Kidney Week

Abstract: SA-PO319

Dietary Salt Modifies the Blood Pressure Response to Renin-Angiotensin Inhibition in Experimental CKD

Session Information

• Hypertension and CVD: Mechanisms
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1403 Hypertension and CVD: Mechanisms

Authors

• Bovee, Dominique M., Erasmus Medical Center, Rotterdam, Netherlands

Dominique M. Bovee,

• Cuevas, Catherina A., Erasmus Medical Center, Rotterdam, Netherlands

Catherina A. Cuevas,

• Danser, Alexander H., Erasmus Medical Center, Rotterdam, Netherlands

Alexander H. Danser,

• Zietse, Robert, Erasmus Medical Center, Rotterdam, Netherlands

Robert Zietse,

• Hoorn, Ewout J., Erasmus Medical Center, Rotterdam, Netherlands

Ewout J. Hoorn,

Background

Salt-sensitive hypertension is a hallmark of chronic kidney disease (CKD). The role of dietary salt and the renin-angiotensin system (RAS) in the pathogenesis of salt-sensitive hypertension in CKD is incompletely understood. Our aim was to dissect the role of dietary salt and the RAS in a rat model of hypertension and CKD.

Methods

Sprague Dawley rats were subjected to 5/6^th nephrectomy, allowed to recover for four weeks, and subsequently subjected to one of four treatments: (1) vehicle, (2) adrenalectomy (Adx), (3) Adx + losartan (30 mg/kg/d), or (4) spironolactone (80 mg/kg/d). These interventions were performed either under normal dietary salt (0.4% NaCl) or high salt (4% NaCl) conditions. Mean arterial pressure (MAP) was measured by radiotelemetry, GFR by transcutaneous FITC-sinistrin clearance, and skin sodium (Na⁺) by flame photometry after dissolving skins in nitric acid and hydrogen peroxide.

Results

5/6^th nephrectomy reduced GFR from 1.3 ± 0.4 to 0.4 ± 0.1 ml/min/100g. On a high salt diet, BP was resistant to RAS intervention, except for an attenuated BP rise in rats receiving spironolactone (Figure). On a normal salt diet, BP kept increasing with vehicle, but stabilized with Adx and spironolactone. Adx + losartan reduced BP remarkably. On a high salt diet, spironolactone prevented Na⁺ accumulation in skin. For all groups, skin Na⁺ correlated positively with heart weight.

Conclusion

High salt increases BP in CKD in part via direct effects on the mineralocorticoid receptor. Under normal salt conditions, however, hypertension in CKD depends on the combined effects of angiotensin II and aldosterone. Dietary salt modifies the BP response to RAS interventions in CKD, and accumulates in the skin. Our observations may have both therapeutic and prognostic implications for human CKD.