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Toll‐like receptor 4 (TLR4) mediates cavernosal dysfunction in diabetic rats
Author(s) -
Nunes Kenia Pedrosa,
CarriloSepulveda Maria Alicia,
Szasz Theodora,
Webb R. Clinton
Publication year - 2013
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.27.1_supplement.1138.6
Subject(s) - medicine , endocrinology , tlr4 , phenylephrine , erectile dysfunction , diabetes mellitus , receptor , contraction (grammar) , stimulation , contractility , vascular smooth muscle , smooth muscle , blood pressure
Vascular abnormalities associated with diabetes mellitus constitute a major cause of erectile dysfunction (ED). The immune system activates toll‐like receptors (TLRs), and increased TLR4 has been found in diabetic patients. We hypothesized that TLR4 mediates vascular dysfunction in diabetic corpus cavernosum (CC) by increasing contractility. Functional experiments using CC tissue from STZ‐induced diabetic rats (65mg/Kg s.c.,5 weeks), western blot analysis and cavernosal vascular smooth muscle cells (VSMC) were used. Results showed that increased CC contraction from adrenergic stimulation with phenylephrine (PE, 10 −9 –10 −4 M) was abolished by a specific TLR4 inhibitor CLI‐095 (10 −5 M; 35′), demonstrating that blockade of this receptor decreases adrenergic sensitivity in diabetic CC (Log EC50: 5.72±0.05 vs. 5.04±0.06, p≤0.05). The maximum contraction elicited by PE (10 −4 M) in diabetic rats plus CLI‐095 was significantly decreased in comparison to that in non‐treated diabetic rats (7.92±0.35 vs. 12.34±0.43 mN respectively). TLR4 was significantly increased in CC from STZ‐induced diabetic rats. Immunofluorescence of cultured cavernosal VSMC stimulated for 12h with high glucose (25mM) suggests that increased TLR4 expression was triggered by hyperglycemia in CC. In conclusion, these results indicate an involvement of TLR4 in impaired erectile function during diabetes.