Cardiovascular and renoprotective effects of renal denervation associated with AT1 receptor antagonism in experimental chronic kidney disease

Chronic kidney disease (CKD) is characterized by progressive and irreversible loss of kidney function. The main causes of CKD are arterial hypertension (AH) and type 2 diabetes. Previous studies by our group showed that renal denervation (DNx) decreased arterial hypertension and sympathetic overactivity in rats with CKD. In the present study, we studied the renoprotective and cardiovascular effects of DNx associated or not with renin-angiotensin system (RAS) blockade. Wistar rats underwent experimental CKD induction (⅚ nephrectomy model). After 4 weeks of CKD induction, we performed DNx and collected data after 4 weeks. Groups that underwent RAS blockade were treated orally with losartan (30mg/kg/day) in the last 4 weeks of the 8-week protocol. Losartan decreased arterial pressure (118±21 mmHg) compared to CKD group (175±18 mmHg). However, the association of losartan treatment with DNx was able to normalize this parameter (94±9mmHg). In addition, losartan normalized baseline renal sympathetic nerve activity, and DNX associated or not with losartan normalized splanchnic sympathetic nerve activity. Interestingly, lipocalin associated with neutrophil gelatinase (NGAL), an important marker of tubular injury, and an intrarenal RAS marker were normalized after DNx associated with losartan treatment (70.9±23.8 NGAL:Cru) or not (66.6±17.8 NGAL:Cru) was normalized. Treatments unchanged water intake or urinary flow. Taken altogether, our data show that despite the association of DNx and RAS blockade produces a further decrease in AH, the improvement in renal function markers and normalization in intrarenal RAS and sympathetic drive is similar after DNx or RAS blockade alone. FINANCIAL SUPPORT: CAPES, FAPESP and CNPq This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.