Cardiac effect of vitamin D receptor modulators in uremic rats

Autor: Ai Yamazaki-Nakazawa, Eriko Kinugasa, Fumiko Kondo, Masahide Mizobuchi, Fumihiko Koiwa, Nozomu Hosaka, Hiroaki Ogata, Takanori Shibata
Rok vydání: 2016
Předmět:
Male
Paricalcitol
medicine.medical_specialty
Cardiotonic Agents
Cardiac fibrosis
Heart Ventricles
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
030232 urology & nephrology
Gene Expression
030204 cardiovascular system & hematology
Nephrectomy
Biochemistry
Calcitriol receptor
Rats
Sprague-Dawley
Transforming Growth Factor beta1
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Calcitriol
Fibrosis
Internal medicine
medicine
Animals
Renal Insufficiency
Molecular Biology
Uremia
Creatinine
Ventricular Remodeling
Chemistry
Cell Biology
medicine.disease
Rats
Fibroblast Growth Factors
Echocardiography
Parathyroid Hormone
Ergocalciferols
Receptors
Calcitriol
Molecular Medicine
Calcium
Secondary hyperparathyroidism
Injections
Intraperitoneal
Kidney disease
medicine.drug
Zdroj: The Journal of Steroid Biochemistry and Molecular Biology. 163:20-27
ISSN: 0960-0760
Popis: Vitamin D receptor (VDR) modulators (VDRMs) are commonly used to control secondary hyperparathyroidism (SHPT) associated with chronic kidney disease, and are associated with beneficial outcomes in cardiovascular disease. In this study, we compared the cardiac effect of VS-105, a novel VDRM, with that of paricalcitol in 5/6 nephrectomized uremic rats. Male Sprague-Dawley rats were 5/6 nephrectomized, fed a standard diet for 4 weeks to establish uremia, and then treated (intraperitoneally, 3 times/week) with vehicle (propylene glycol), paricalcitol (0.025 and 0.15μg/kg), or VS-105 (0.05 and 0.3μg/kg) for 4 weeks. In uremic rats, neither VDRM (low and high doses) altered serum creatinine and phosphorus levels. Serum calcium was significantly higher with high dose paricalcitol compared to sham rats. PTH levels were significantly decreased with low dose paricalcitol and VS-105, and were further reduced in the high dose groups. Interestingly, serum FGF23 was significantly higher with high dose paricalcitol compared to sham rats, whereas VS-105 had no significant effect on FGF23 levels. Left ventricle (LV) weight and LV mass index determined by echocardiography were significantly suppressed in both high dose VDRM groups. This suppression was more evident with VS-105. Western blotting showed significant decreases in a fibrosis marker TGF-β1 in both high dose VDRM groups (vs. vehicle) and Masson trichrome staining showed significant decreases in cardiac fibrosis in these groups. These results suggest that VS-105 is less hypercalcemic than paricalcitol and has favorable effects on SHPT and cardiac parameters that are similar to those of paricalcitol in uremic rats. The cardioprotective effect is a noteworthy characteristic of VS-105.
Databáze: OpenAIRE
Externí odkaz: