Effects of proANP31-67 in a preclinical model of uninephrectomy and cardiac ischemia/reperfusion injury: cardiac remodeling and tissue biochemical profiling

Concomitant cardiac and renal dysfunction represent a clinically relevant condition with limited therapeutic options. This study examined the effects of the linear ANP fragment proANP31-67 in a preclinical model combining unilateral nephrectomy (UNX) and cardiac ischemia/reperfusion (I/R) injury. Wistar rats underwent UNX followed by I/R and were randomized to receive proANP31-67 or vehicle for four weeks. Cardiac structure and function were evaluated by echocardiography and isolated cardiomyocyte analyses. Fourier-transform infrared (FTIR) spectroscopy was used to assess biochemical composition in cardiac and renal tissue as well as urine. Chronic UNX induced diastolic impairment with preserved systolic function, which was further aggravated by I/R. proANP31-67 prevented systolic deterioration, reduced myocardial fibrosis, attenuated cardiomyocyte hypertrophy, and improved Ca2+ handling, independent of blood pressure. FTIR imaging identified distinct cardiac (amino acid-, collagen-, and carbohydrate-associated) and renal (free amino acid-, protein-, and lipid-associated) spectral features across experimental groups. Conventional renal indices, including albumin-to-creatinine ratio and 24-hour protein excretion, remained unchanged; however, vibrational spectroscopy detected subtle biochemical alterations in renal tissue and urine that were modulated by proANP31-67. In this model of reduced nephron mass with superimposed cardiac injury, proANP31-67 exerted marked cardioprotective effects and was associated with coordinated changes in tissue biochemical signatures, supporting further investigation of its therapeutic potential.