Abstract: FR-PO206

Effect of Spironolactone on a Transgenic Rat Model of Hypertension and Myocardial Infarction

Session Information

Category: Hypertension

  • 1103 Vascular Biology and Dysfunction

Authors

  • Leader, Catherine, University of Otago, Dunedin, New Zealand
  • Sammut, Ivan Andrew, University of Otago, Dunedin, New Zealand
  • Wilkins, Gerard T., University of Otago, Dunedin, New Zealand
  • Walker, Robert J., University of Otago, Dunedin, New Zealand
Background

Hypertension contributes to heart disease and renal injury. However the impact of MI plus hypertension on renal injury is not clearly described. Spironolactone (SP) can reduce cardiac fibrosis and improve cardiac re-modelling post MI; its effects on the kidney are unknown. We examined the effects of SP on renal fibrosis in hypertensive rats post MI.

Methods

Ffive groups of adult male Cyp1a1Ren2 rats: normotensive (N), hypertensive (H), hypertensive fed SP daily (50 mg day-1) (H-SP), hypertensive with MI (left anterior coronary ligation) (H-MI) and hypertensive with MI plus daily SP (H-MI-SP). Hypertension (>160 mmHg systolic) was induced by 0.167 % (w/w) indole-3-carbinol added to the rat chow. Systolic blood pressure (SBP) and echocardiograms were recorded at termination, 28 days after MI. Cardiac and renal tissue was harvested for analysis.

Results

SBP was only reduced in the H-MI group (p=0.05) compared with all the other H groups (155±24 and 173±11mmHg respectively). SBP was not significantly reduced by SP in either of the treated groups. Ejection fraction (EF) was significantly reduced in all animals with MI (42±10%), addition of SP had no effect (43±10%). The Glomerulosclerosis Index (GSI) in normals was 0.2±0.1 and was significantly higher in all hypertensive groups (p>0.001). The H-SP group (0.9±0.04) showed a significant decrease in GSI from H controls (1.2±0.07) (p=0.002). The GSI in H-MI-SP (1±0.1) was significantly decreased from the H-MI group (1.3±0.1) (p=0.04). The degree of cortical interstitial fibrosis in all hypertensive groups was not modified by SP.
Figure 1: PAS cortex pictures of representatives from each experimental groups. Scale bar is 200µm.

Conclusion

Conclusion: Severe hypertension caused extensive renal glomerulosclerosis and interstitial fibrosis. SP showed no effect on SBP or EF, but significantly improved GSI scores in hypertensive animals and post MI. SP did not reduce renal interstitial fibrosisl. Further work will aim to define the relation between cardiac injury and renal damage.