# UNI‐494 treatment improves measures of renal dysfunction and cardiac pathology in male rats receiving L‐NAME and angiotensin II

## TL;DR

UNI-494 improves kidney and heart health in rats with induced disease, without affecting blood pressure.

## Contribution

UNI-494 is a novel compound shown to reduce cardiorenal damage in a preclinical model.

## Key findings

- UNI-494 reduced albuminuria and KIM-1 levels in rats with induced kidney damage.
- Cardiac injury was significantly improved with UNI-494 treatment.
- Blood pressure remained unaffected by UNI-494 administration.

## Abstract

Mitochondrial dysfunction is essential in the pathophysiology of both cardiovascular disease (CVD) and chronic kidney disease (CKD). Nicorandil, a nicotinamide nitrate derivative, has been used for years as a cardioprotective agent. It binds to sulfonylurea receptors, activating mitochondrial ATP‐sensitive potassium channels (MitoKATP) and functioning as a Nitric Oxide (NO) donor. However, its clinical use is limited by gastrointestinal complications. UNI‐494 is a novel nicotinamide ester derivative and selective MitoKATP channel activator that reverses mitochondrial dysfunction by closing the mitochondrial permeability transition pore (mPTP) and has renoprotective effects. However, its impact on preclinical models of cardiac and renal disease is unknown. Rodents given N
ω‐nitro‐L‐arginine methyl ester (L‐NAME) to suppress NO synthase and angiotensin II (AngII) show substantial cardiac and renal damage with significant increases in blood pressure. We hypothesize that mitochondrial dysfunction contributes to the pathophysiology of cardiorenal damage in the L‐NAME/AngII rat model and that UNI‐494 would improve cardiovascular and renal parameters. We studied the in vivo impact of UNI‐494 on cardiorenal damage in the L‐NAME/AngII rat model. Treatment with UNI‐494 significantly reduced L‐NAME/AngII‐induced albuminuria, KIM‐1 levels, and cardiac injury, with no significant effect on blood pressure. Our data suggest that cardiorenal damage can be prevented by treatment with UNI‐494.