Zhenwu Decoction Attenuates Water-Retention-Related Phenotypes and Multiorgan Injury in Rats With Doxorubicin-Induced Chronic Heart Failure.

OBJECTIVE

This study is aimed at evaluating the effects of Zhenwu Decoction (ZWD) on cardiac dysfunction, water-retention-related phenotypes, and brain and kidney injury in rats with doxorubicin-induced chronic heart failure (CHF), and at examining whether these effects were accompanied by changes in AVP, V2R, PKA-Cα, and AQP2-related markers.

METHODS

Rats that met the prespecified CHF criteria after doxorubicin administration were rerandomized to the model, ZWD-L, ZWD-M, ZWD-H, or tolvaptan groups and treated once daily for 14 consecutive days. Cardiac function, biochemical and water balance-related outcomes, histopathology, brain AVP, and renal V2R, PKA-Cα, and AQP2 expression were assessed. The animal was the experimental unit, and the number analyzed is reported for each outcome.

RESULTS

Compared with the control group, model rats showed impaired cardiac function; increased ascites and tissue water retention; reduced 24-h urine output; histological injury in the heart, brain, and kidney; and altered AVP, V2R, PKA-Cα, and AQP2-related markers. ZWD treatment was associated with improvement in these measured outcomes, with the magnitude and statistical support varying across doses. Tolvaptan produced the expected aquaretic reference response. Adjusted p values and the number of animals analyzed are reported for each outcome.

CONCLUSION

In this doxorubicin-induced CHF model, ZWD improved cardiac function and water-retention-related phenotypes and was accompanied by changes in AVP, V2R, PKA-Cα, and AQP2-related markers. These data support an association but do not establish pathway mediation, direct target engagement, or heart-brain-kidney crosstalk.