ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-OR077

Myocardial Infarction in an Inducible Hypertensive Rat Model: Does Spironolactone Reduce Renal Fibrosis?

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Leader, Catherine, University of Otago, Dunedin, New Zealand
  • Walker, Robert J., University of Otago, Dunedin, New Zealand
Background

Hypertension is a leading cause of myocardial infarction (MI), and is strongly associated with renal injury. However, superposition of MI on renal injury secondary to hypertension is not clearly defined. Likewise mineralocorticoid blockade (e.g. spironolactone; SP) has been shown to reduce cardiac fibrosis and improve cardiac outcomes post MI, but consequences for renal function are not known. We aimed to explore the effects of SP on renal fibrosis, post MI, in established hypertensive rats.

Methods

Hypertension was induced and maintained using male Cyp1a1Ren2 rats (n=20) by addition of 0.167% (w/w) indole-3-carbinol to the rat chow, and established for two weeks prior to treatment or surgical intervention. Rats (10 weeks of age) were divided into four groups: hypertensive controls (H), hypertensive controls fed SP daily (4.4mg/kg/day; H-SP), hypertensive with MI (permanent left anterior coronary ligation; H-MI) and H-MI plus daily SP (H-MI-SP). Physiological data and tissue was collected four weeks after MI for analysis.

Results

Systolic blood pressure (SBP) did not differ significantly between groups. Ejection fraction (EF) was significantly (p<0.001) reduced by MI induction (42±10%), but not improved by SP treatment (43±10%). MI significantly increased global cardiac fibrosis (2.2±0.5%) and renal cortical fibrosis (3.1±0.9%) when compared to hypertensive animals (1.3±0.5% and 2.6±0.9% respectively), while SP therapy post infarct significantly reduced cardiac interstitial fibrosis (1.5±0.6%) and kidney cortical fibrosis (1.4±0.6%). The reduction in fibrosis was associated with decreased expression of αSMA, TGFβ, reduced expression of MCP1 and a significant reduction in interstitial macrophages. SP significantly reduced (p<0.01) glomerulosclerosis in both H-SP group (from 1.2±0.07 in hypertensive controls to 0.9±0.04) and from 1.5±0.1 (H-MI) to 1.2±0.2 in the H-MI-SP group.

Conclusion

The addition of MI significantly worsened the extent of hypertension-induced renal fibrosis and glomerulosclerosis. SP treatment resulted in significant improvement in renal fibrosis and GSI scores in hypertensive animals with or without MI. Further work will aim to further define the relationship between cardiac injury and renal damage.