Ischemic preconditioning protects the heart against ischemia-reperfusion injury in chronic kidney disease in both males and females

Highlights 1. There was no difference in the severity of chronic kidney disease (CKD) between male and female rats based on serum urea and creatinine levels as well as creatinine clearance. 2. As compared to females, males developed a more severe uremic cardiomyopathy characterized by left ventricular hypertrophy and fibrosis in CKD based on echocardiography and histology. 3. Following ischemia/reperfusion, infarct size was significantly smaller in females than in males, both in the sham-operated and CKD groups. 4. The infarct size-limiting effect of ischemic preconditioning (IPRE) was preserved in both sexes in CKD despite the more severe uremic cardiomyopathy in male CKD rats. 5. IPRE significantly increased the phospho-STAT3/STAT3 ratio in sham-operated, but not in CKD animals in both sexes

The kisspeptin-1 receptor antagonist peptide-234 aggravates uremic cardiomyopathy in a rat model

Abstract Uremic cardiomyopathy is characterized by diastolic dysfunction, left ventricular hypertrophy (LVH), and fibrosis. Dysregulation of the kisspeptin receptor (KISS1R)-mediated pathways are associated with the development of fibrosis in cancerous diseases. Here, we investigated the effects of the KISS1R antagonist peptide-234 (P234) on the development of uremic cardiomyopathy. Male Wistar rats (300–350 g) were randomized into four groups: (i) Sham, (ii) chronic kidney disease (CKD) induced by 5/6 nephrectomy, (iii) CKD treated with a lower dose of P234 (ip. 13 µg/day), (iv) CKD treated with a higher dose of P234 (ip. 26 µg/day). Treatments were administered daily from week 3 for 10 days. At week 13, the P234 administration did not influence the creatinine clearance and urinary protein excretion. However, the higher dose of P234 led to reduced anterior and posterior wall thicknesses, more severe interstitial fibrosis, and overexpression of genes associated with left ventricular remodeling (Ctgf, Tgfb, Col3a1, Mmp9), stretch (Nppa), and apoptosis (Bax, Bcl2, Casp7) compared to the CKD group. In contrast, no significant differences were found in the expressions of apoptosis-associated proteins between the groups. Our results suggest that the higher dose of P234 hastens the development and pathophysiology of uremic cardiomyopathy by activating the fibrotic TGF-β-mediated pathways