Cardioprotective effect of abscisic acid in a rat model of type 3 cardio-renal syndrome: Role of NOX-4, P-53, and HSP-70

Cardiorenal syndrome (CRS) is a complex heart and kidney pathophysiologic disorder that leads to a bidirectional interrelationship between them. Abscisic acid (ABA) is a phytohormone that is present in plants, and is known to regulate fundamental physiological functions. This study aimed to explore the efficacy of ABA in surgically induced-CRS type 3 rats. Rats were randomly and equally divided into four groups. Rats in Group 1 received saline (Sham group), Group 2 included control induced-CRS rats, Group 3 rats (CRS+ABA) included CRS rats treated with ABA and Group 4 (CRS + ABA + Verapamil + propofol) were CRS rats treated with Verapamil, propofol and ABA. The rats were treated with the drugs daily for four weeks. At the end of the study, relative heart weight corrected QT interval (QTc), mean blood pressure (MBP), kidney functions, oxidative stress, NADPH oxidase 4 (NOX4), protein 53 (P53), and heat shock proteins-70 (HSP-70) expression was assessed and recorded. ABA led to a significant shortening of the ventricular action potential duration indicated by QTc. Furthermore, it significantly lowered heart weight, MBP, serum creatinine, NOX-4, and P-53 expression and augmented HSP-70 expression. In contrast, adding calcium channel blockers (CCBs) to ABA mitigated this effect. The results suggested that ABA has a potential protective role in CRS-induced cardiac hypertrophy and arrhythmia that could be mediated through inhibition of P-53, NOX-4, and an increase in HSP-70 expression.