Morphometric and Functional Evaluation of Nonrenal Vasculature in Female and Male PKD/Mhm (Cy/+) Rats

Kidney & Blood Pressure Research · Published 2026-01-30 · DOI 10.1159/000550553

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Abstract

Introduction: Polycystic kidney disease (PKD) is a genetic disorder characterized by renal enlargement due to cyst formation. Besides cystic complications, patients with autosomal dominant PKD (ADPKD) can develop vascular abnormalities. We investigated the impact of ADPKD on aortic morphometry and function in female and male PKD rats. Methods: Thoracic aortic rings were obtained from six-month-old female (n = 10; 307 ± 4 g) and male (n = 10; 470 ± 24 g) PKD/Mhm (Cy/+) rats, as well as age-matched control female (n = 9; 312 ± 6 g) and control male (+/+) (n = 13; 460 ± 14 g) rats. Vascular function was evaluated ex vivo using organ baths. Biomarkers of renal function were evaluated, and histology was performed. Results: PKD female and PKD male rats showed elevated serum creatinine levels compared to their respective controls (PKD female: 50.0 ± 1.7 μmol/L vs. control female: 43.9 ± 2.1 μmol/L; PKD male: 178.7 ± 21.0 μmol/L vs. control male: 40.4 ± 1.3 μmol/L, p < 0.05), and these levels were found to be higher in the PKD males than in the PKD females (p < 0.0001). Endothelial dysfunction, characterized by reduced maximum relaxation to acetylcholine, was observed in the PKD males compared to control males (55 ± 2% vs. 77 ± 1%, p < 0.05). Additionally, contractile responses to phenylephrine and high potassium were decreased in PKD male compared to control male. Morphometric analysis revealed increased wall thickness, wall cross-sectional area normalized to body weight, and wall:lumen area ratio in PKD male aortas compared to control male. Additionally, PKD male showed increased cleaved poly(ADP-ribose) polymerase-1 immunoreactivity compared to control males. All these parameters were unchanged in PKD females compared to control females. Conclusion: Six-month-old male rats with PKD, but not females, display endothelial dysfunction, impaired smooth muscle contraction/relaxation, pathological changes in aortic morphometry, and increased apoptosis, providing a model for studying vascular complications in ADPKD.

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Publication details

Year
2026

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