Abstract: PO1826
Contributions of Obesity and Hypertension to Progression of Cardiorenal Syndrome in Non-Diabetic Obese Female ZSF1 Rats
Session Information
- Hypertension and CVD: Mechanisms
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Nguyen, Isabel T.N., Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands
- Joles, Jaap A., Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands
- Verhaar, Marianne C., Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands
Background
Obesity and hypertension are highly prevalent in patients with cardiorenal syndrome (CRS). Insight in how these comorbidities individually contribute to disease progression is required to improve treatment strategy. We dissected the separate contribution of obesity and worsening hypertension by deoxycorticosterone acetate (DOCA) plus high salt diet in the obese female ZSF1 rat, a model of metabolic CRS in the absence of diabetes [Nguyen, PLoS One 2020]. We hypothesize that in obese non-diabetic female ZSF1 rats obesity has a profound effect on functional progression of CRS while hypertension mainly affects fibrosis and inflammation.
Methods
Systolic blood pressure (SBP), renal and cardiac function were assessed biweekly in lean and obese female ZSF1 rats from 12 to 26 weeks of age. From 19 weeks, rats were implanted with either a DOCA pellet and fed a high salt (6% w/w) diet or with a placebo pellet and fed a normal salt diet. At 26 weeks of age, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were assessed under isoflurane anesthesia. Subsequently, rats were sacrificed and tissues processed for analysis of renal and cardiac damage and inflammation.
Results
Obese versus lean placebo rats showed elevated E/e’ ratio from 12 weeks, indicative of diastolic dysfunction. From 24 weeks obese compared to lean placebo rats developed proteinuria with lower GFR at 26 weeks of age. DOCA-salt markedly increased SBP in obese but not lean rats, despite similarly high natriuresis compared to placebo rats. ERPF was increased by DOCA-salt in lean but not obese rats. DOCA-salt worsened proteinuria and glomerulosclerosis in obese rats. Cardiac fibrosis and glomerular hypertrophy, present in obese rats, were not aggravated by DOCA-salt. However, DOCA-salt increased the number of macrophages in heart, but not in glomeruli of obese ZSF1 rats.
Conclusion
Obesity leads to renal and cardiac dysfunction and damage in female ZSF1 rats. Even without worsening of hypertension (DOCA+salt), cardiac dysfunction preceded proteinuria, suggestive of CRS type 2. Our findings suggest that antihypertensive and antiproteinuric treatment at a later stage without initially addressing metabolic risk, even in the absence of diabetes, will not provide adequate functional protection in CRS type 2.
Funding
- Private Foundation Support