Therapeutic Effects of Sacubitril/Valsartan and Dapagliflozin on Oxidative Stress and Iron Dysregulation in Monocrotaline-Induced Pulmonary Arterial Hypertension

Presenter: Wei-Chun Huang

Pulmonary arterial hypertension (PAH) remains a progressive disease with limited therapeutic options, and although sacubitril/valsartan and dapagliflozin show promise in cardiovascular protection, their effects in experimental PAH are unclear. In Sprague-Dawley rats with monocrotaline-induced PAH, investigators compared sacubitril/valsartan alone, dapagliflozin alone and the combination, measuring plasma reduced glutathione, total glutathione, malondialdehyde and ferritin to assess systemic oxidative stress and iron metabolism. PAH was accompanied by a marked fall in reduced glutathione and significantly elevated ferritin, indicating oxidative stress and iron dysregulation. Either drug alone partially restored reduced glutathione and attenuated the ferritin rise, while combination therapy showed a more consistent antioxidative profile. Total glutathione and malondialdehyde did not differ among groups, suggesting the treatments mainly modulated redox balance rather than total glutathione content. All three regimens mitigated oxidative imbalance and abnormal iron metabolism, with possible additive benefit from the combination; the authors see potential for combined sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT2) inhibition as an adjunct strategy in PAH.

American Heart Association (AHA) Scientific Sessions 2026, November 6–9, Chicago, Illinois