Sodium Glucose Co-Transporter 2 Inhibitors Improve Renal Congestion and Left Ventricular Fibrosis in Rats With Hypertensive Heart Failure

• Published in: Circulation Journal Vol. 86; no. 12; pp. 2029 - 2039
• Main Authors: Nakatsukasa, Tomofumi, Ishizu, Tomoko, Ouchi, Masumi, Murakoshi, Nobuyuki, Sato, Kimi, Yamamoto, Masayoshi, Kawanishi, Kunio, Seo, Yoshihiro, Ieda, Masaki
• Format: Journal Article
• Language: English
• Published: The Japanese Circulation Society 25.11.2022
• Subjects: Cardio-renal syndrome; Congestive heart failure; Left ventricular hypertrophy; Renal congestion; SGLT2 inhibitor
• ISSN: 1346-9843; 1347-4820; 1347-4820
• DOI: 10.1253/circj.CJ-22-0105

Background: Elevated central venous pressure (CVP) in heart failure causes renal congestion, which deteriorates prognosis. Sodium glucose co-transporter 2 inhibitor (SGLT2-i) improves kidney function and heart failure prognosis; however, it is unknown whether they affect renal congestion. This study investigated the effect of SGLT2-i on the kidney and left ventricle using model rats with hypertensive heart failure.Methods and Results: Eight rats were fed a 0.3% low-salt diet (n=7), and 24 rats were fed an 8% high-salt diet, and they were divided into 3 groups of untreated (n=6), SGLT2-i (canagliflozin; n=6), and loop diuretic (furosemide; n=5) groups after 11 weeks of age. At 18 weeks of age, CVP and renal intramedullary pressure (RMP) were monitored directly by catheterization. We performed contrast-enhanced ultrasonography to evaluate intrarenal perfusion. In all high-salt fed groups, systolic blood pressure was elevated (P=0.287). The left ventricular ejection fraction did not differ among high-salt groups. Although CVP decreased in both the furosemide (P=0.032) and the canagliflozin groups (P=0.030), RMP reduction (P=0.003) and preserved renal medulla perfusion were only observed in the canagliflozin group (P=0.001). Histological analysis showed less cast formation in the intrarenal tubule (P=0.032), left ventricle fibrosis (P<0.001), and myocyte thickness (P<0.001) in the canagliflozin group than in the control group.Conclusions: These results suggest that SGLT2-i causes renal decongestion and prevents left ventricular hypertrophy, fibrosis, and dysfunction