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- Title
Elevated ceruloplasmin impairs vascular endothelial function in diabetes.
- Authors
Chitaley, Kanchan; Luttrell, Ian P.; Karen, Engel; King, Stephen H.; Leah, Harris Z.; Wessells, Hunter
- Abstract
Erectile dysfunction is a harbinger of cardiovascular disease. The pro-oxidant, copper-transporter, ceruloplasmin (CP), is elevated in diabetic patients and rodents. In this study, we tested the hypothesis that CP impairs penile endothelium-dependent dilation in diabetes. Cp-deficient (Cp-/-) and wild-type (Wt) mice (2-3 mo) were treated with streptozotocin (STZ; 100mg/kg, i.p., 2 days) or citrate buffer (CNT). After 6-8 wks, blood glucose and CP expression were measured, and cavernosal relaxation to acetylcholine (ACh) assessed by myography. In additional studies, CP (3 µg/µl in 50µl) was administered intracorporally into Wt mice. Intracavernosal pressure/mean arterial pressure (ICP/MAP) to electrical stimulation of the cavernous nerve was assessed prior to and after CP injection. ACh relaxation did not change in non-diabetic, Wt-CNT vs. Cp-/--CNT, mice. STZ increased blood glucose in both groups. Penile CP expression was elevated in STZ vs. CNT-treated Wt mice. Maximum ACh relaxation (10µM) was significantly decreased in STZ-treated Wt mice vs. Wt-CNT (50±5 vs. 65±2%), but not in Cp-/--STZ vs. Cp-/--CNT mice (68±3 vs. 66±7%). Further, injection of CP significantly blunted ICP/MAP (mean change in area under the curve after CP or vehicle: 25±6.4 vs. -0.4±3.2, respectively). Altogether, these loss and gain of function data support the hypothesis that CP impairs penile vascular endothelial function in diabetes.
- Subjects
CERULOPLASMIN; DIABETES; IMPOTENCE; STREPTOZOTOCIN; ACETYLCHOLINE; BLOOD sugar
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA1196
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.6.a1196-b