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Rolipram improves renal perfusion and function during sepsis in the mouse
Joseph H Holthoff1, Zhen Wang, Naeem K Patil
1Department of Pharmacology and Toxicology (J.H.H, Z.W., N.K.P., P.R.M.) and Pathology (N.G.), University of Arkansas for Medical Sciences, Little Rock, Arkansas.
The Journal of Pharmacology and Experimental Therapeutics
|September 11, 2013
Summary
Rolipram, a PDE4 inhibitor, improved kidney function and microcirculation in septic mice. Delayed treatment also preserved kidney function, suggesting potential for treating sepsis-induced acute kidney injury.
Area of Science:
- Nephrology
- Pharmacology
- Critical Care Medicine
Background:
- Sepsis-induced microcirculatory dysfunction contributes to acute kidney injury (AKI) and mortality.
- Phosphodiesterase 4 (PDE4) inhibition with rolipram may improve microvascular permeability and renal blood flow (RBF).
Purpose of the Study:
- To investigate the efficacy of rolipram in improving renal microcirculation and function during sepsis using a murine model.
Main Methods:
- Sepsis was induced in mice using cecal ligation and puncture (CLP).
- Rolipram was administered at varying doses (0.3-10 mg/kg) to assess acute effects.
- Delayed treatment with rolipram was administered 6 hours post-CLP.
Main Results:
- Rolipram acutely restored capillary perfusion and increased RBF in a dose-dependent manner, with 1 mg/kg being the most effective.
- Rolipram reduced renal microvascular permeability.
- Delayed rolipram treatment improved renal function, indicated by reduced blood urea nitrogen and serum creatinine, and increased glomerular filtration rate, despite no reduction in nitric oxide markers.
Conclusions:
- Restoring microcirculation with rolipram, even with delayed administration, can improve renal function in sepsis-induced AKI.
- PDE4 inhibitors warrant further investigation for treating septic AKI.