THE EFFECT OF SPIRONOLACTONE ON RENAL INJURY (FIBROSIS) IN A HYPERTENSIVE TRANSGENIC CYP1A1REN2 RAT MODEL.

C LEADER1, M MOHARRAM1, I SAMMUT1,  S COFFEY1, G WILKINS1, R WALKER1
1University Of Otago, Dunedin, New Zealand

Aim:  To investigate the impact of chronic hypertension with and without daily spironolactone (SP) on heart and kidney function and injury in a rat model of hypertension.
Background:  Hypertension is one of the leading contributors to cardiovascular and renal disease.   Spironolactone (SP) improves cardiac outcomes following injury, but its impact on hypertension-induced kidney fibrosis is uncertain.
Methods:  Male Cyp1a1Ren2 rats were randomised to normal chow or chow with addition of 0.167% indol-3-carbinol to induce hypertension (>150mmHg).  Hypertensive rats were further divided into those receiving spironolactone 50mg daily or not.  Systolic blood pressure (SBP), urine collection and echocardiograms were performed before termination (after three months) and tissue collected for analyses. The extent of fibrosis was determined on Masson’s trichrome stained sections using pixel counts (ImageJ). Glomerulosclerosis was scored semi-quantitatively on PAS sections.
Results: Chronic hypertension resulted in elevated SBP (196±19 vs 91±12 mmHg (controls)), proteinuria (60±19 vs 14±3 ml.kg-1.hr-1), cortical fibrosis (7±0.4% vs 0.2±0.1%) and glomerulosclerosis index scores (GSI: 2.6±0.3 vs 0.2±0.06) [all variables were significant at p<0.001]. Hypertension also reduced cardiac ejection fraction (EF, 67±7 vs 80±3%, p<0.001) and endocardial global longitudinal strain (endoGLS, -19±3 vs -28±3%, p<0.001) compared to normotensive animals.
SP had no impact on SBP, proteinuria, EF or endoGLS, but did result in significant reductions to cortical fibrosis (3±1.3%, p<0.05) and GSI (2±0.1, p<0.05) when compared to hypertensive alone animals.
Conclusions: Chronic elevation of SBP caused significant renal damage over three months.  The addition of spironolactone did not improve physiological measurements but did reduce fibrotic and sclerotic damage in the kidney.  Further work will aim to analyse the relationship between hypertension and renal deterioration.


Biography:
Catherine completed a Master’s degree in Biological Science, exploring the bat-moth arms race, studying the neuroethology of two endemic New Zealand moth species to endemic New Zealand bat calls.  Following this, Catherine developed a keen interest in the medical research field, with specific interest in cardiology, circulation and nephrology. More recently, she completed her PhD (under the supervision of Professor R. Walker) at the University of Otago (New Zealand), investigating the effect of a mineralocorticoid receptor antagonist (Spironolactone) on renal fibrosis following a myocardial infarction in a transgenic hypertensive rat model.

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