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Dantrolene Improves Endothelial Function in Type‐1 Diabetic Rats by Decreasing Oxidative Stress
Author(s) -
Roman Marie,
Alemar Stephanie,
Zack Richard,
Matias Jonathan,
Morales Myrna,
Torres Hector,
Quidgley Jose,
Crespo Maria J
Publication year - 2017
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.31.1_supplement.883.13
Subject(s) - dantrolene , dantrolene sodium , sodium nitroprusside , medicine , endocrinology , oxidative stress , phenylephrine , vasoconstriction , ryanodine receptor , malondialdehyde , acetylcholine , streptozotocin , diabetes mellitus , anesthesia , nitric oxide , calcium , blood pressure
Diabetic patients have a high risk of developing cerebral vasospasms (CVSP). Experimental evidence indicates that the addition of the ryanodine receptor (RyR) blocker dantrolene to standard therapies reduces vasoconstriction in non‐diabetic patients with CVSP. Whether diabetics with CVSP also benefit from this drug, however, is unknown. In this study, we evaluated the effects of a 30‐minute incubation period with dantrolene (50 μM) on acetylcholine (ACh)–induced relaxation in phenylephrine (PHE)‐precontracted aortic rings from streptozotocin (STZ)‐induced Type‐1 diabetic rats. Age‐matched non‐diabetic rats were used as controls (CT). Concentration response curves for the ACh‐induced relaxation from 0.1 nM to 10 μM were performed on aortic rings in the presence and absence of dantrolene. The oxidative‐stress markers malondialdehyde (MDA) and 4‐hydroxyalkenal (4‐HAE) were also measured in aortic homogenates after a 30‐minute incubation period with dantrolene. The E MAX value for the ACh‐induced relaxation was reduced in diabetic rats (40.97 ± 1.92%) when compared to CT (75.74 ± 5.27%) (N=5, P<0.05) without changing the EC 50 value. Acute incubation of aortic rings with 50 μM dantrolene increased the E MAX value in diabetic rats to 70.39 ± 13.84 % (N=5, P<0.05), without affecting this parameter in CT. Endothelium‐independent relaxation with 10 μM sodium nitroprusside (SNP) was not affected by dantrolene in either diabetic or CT rats. In addition, dantrolene decreased MDA +4‐HAE (μM/g protein) in the vasculature of diabetic rats from 3.19 ± 1.15 to 1.16 ± 0.10 (N=5, P<0.05). Together, our results suggest that by reducing oxidative stress and improving endothelial function, dantrolene may exert a beneficial effect in diabetic patients with CVSP by reducing arterial tone. Support or Funding Information Supported by RCMI Grant G12‐RR03051.