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Endothelin‐A receptor antagonist normalizes altered cardiac function and VEGF expression in diabetic rats
Author(s) -
Jesmin Subrina,
Mowa Chishimba,
Newell Allison,
Zaedi Sehel,
Shimoj Nobutake,
Miyauchi Takashi
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a760-d
Alteration in VEGF signaling, a key angiogenic factor, has been documented in inadequate collateral formation in the heart of diabetic (DM) animals and patients. However, no study yet has focused on the therapeutic potential of correcting the defect in VEGF signaling on the heart of DM animals and or patients. Here, we investigate whether administration of a selective ET‐A receptor antagonist (TA‐0201, 1 mg/kg/day) would normalize diminished cardiac VEGF signaling in the early phase of streptozotocin (STZ)‐induced diabetes. Male Sprague‐Dawley rats were administered citrate saline (vehicle) or STZ (65 mg/kg IP). Diabetes was confirmed by hyperglycemia and after 1 week of diabetes, animals were separated into those receiving TA‐0201 or vehicle by osmotic mini pump for 4 weeks. VEGF levels in DM heart were significantly decreased (7.6 ±0.9, pg/mg) than in non‐DM rats (12.3 ±1.3, pg/mg), and TA‐0201 treatment completely normalized the diminished levels of VEGF in DM hearts (12.7 ±2.8, pg/mg). The percentage of fractional shortening (%FS) was decreased in DM heart and was greatly improved by ET antagonism. Nitric oxide levels were increased in DM heart and were kept higher by ET antagonism. However, ET antagonism did not alter higher plasma glucose or lower insulin level in DM rats. The present study is the first to demonstrate a therapeutic potential for preserving myocardial microvasculature in DM using ET antagonist, which may, in turn, block or prevent the development of DM‐related cardiac complications. Sponsor: MONBUSHO.