The online version of this article (doi:10.1186/1475-2840-11-58) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
ES performed the experiments, drafted the manuscript, and performed the statistical analysis. TP participated in designing the study and performing the experiments. ES, PK, JK, MZ, JE conceived of the study, participated in its design and coordination, and helped to draft the manuscript. MB and APA analysed the data, participated in the study design and coordination, and helped to draft the manuscript. MA and AA performed the histological analyses and helped to draft the manuscript. All authors have read and approved the final manuscript.
Diabetes mellitus is associated with micro- and macrovascular complications and increased cardiovascular risk. Elevated levels of serum asymmetric dimethylarginine (ADMA) may be responsible for endothelial dysfunction associated with diabetes-induced vascular impairment. Vitamin D may have potential protective effects against arterial stiffening. This study aimed to examine both the effects of diabetes on the functional/structural properties of the aorta and the endothelial function and the effects of vitamin D supplementation.
Male Wistar rats (n = 30) were randomly assigned to control untreated, diabetic untreated, and diabetic + cholecalciferol groups. Diabetes was induced by intraperitoneal injection of streptozotocin, followed by oral administration of cholecalciferol (500 IU/kg) for 10 weeks in the treatment group. Aortic pulse wave velocity (PWV) was recorded over a mean arterial pressure (MAP) range of 50 to 200 mmHg using a dual pressure sensor catheter. Intravenous infusion of phenylephrine and nitroglycerine was used to increase and decrease MAP, respectively. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using a radioimmune assay. ADMA levels in serum were measured by enzyme-linked immunoassay. Aortic samples were collected for histomorphometrical analysis.
PWV up to MAP 170 mmHg did not reveal any significant differences between all groups, but in diabetic rats, PWV was significantly elevated across MAP range between 170 and 200 mmHg. Isobaric PWV was similar between the treated and untreated diabetic groups, despite significant differences in the levels of serum 25(OH)D (493 ± 125 nmol/L vs 108 ± 38 nmol/L, respectively). Serum levels of ADMA were similarly increased in the treated and untreated diabetic groups, compared to the control group. The concentration and integrity of the elastic lamellae in the medial layer of the aorta was impaired in untreated diabetic rats and improved by vitamin D supplementation.
PWV profile determined under isobaric conditions demonstrated differential effects of uncontrolled diabetes on aortic stiffness. Diabetes was also associated with elevated serum levels of ADMA. Vitamin D supplementation did not improve the functional indices of aortic stiffness or endothelial function, but prevented the fragmentation of elastic fibers in the aortic media.
Mayer O, Filipovský J, Seidlerová J, Vaněk J, Dolejšová M, Vrzalová J, Cífková R: The association between low 25-hydroxyvitamin D and increased aortic stiffness. J Hum Hypertens. 2011, doi:10.1038/jhh.2011.94.
Targher G, Bertolini L, Padovani R, Zenari L, Scala L, Cigolini M, Arcaro G: Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness among type 2 diabetic patients. Clin Endocrinol. 2006, 65: 593-597. 10.1111/j.1365-2265.2006.02633.x. CrossRef
Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R: The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in Type 2 diabetic patients. Int J Clin Pract. 2003, 57: 258-261. PubMed
Ng K, Hildreth CM, Phillips JK, Avolio AP: Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model. Am J Physiol Renal Physiol. 2011, 300: 1431-1436. 10.1152/ajprenal.00079.2011. CrossRef
Wolffenbuttel BH, Boulanger CM, Crijns FR, Huijberts MS, Poitevin P, Swennen GN, Vasan S, Egan JJ, Ulrich P, Cerami A, Levy BI: Breakers of advanced glycation end products restore large artery properties in experimental diabetes. Proc Natl Acad Sci USA. 1998, 95: 4630-4634. 10.1073/pnas.95.8.4630. PubMedCentralCrossRefPubMed
Resch M, Schmid P, Amann K, Fredersdorf S, Weil J, Schach C, Birner C, Griese DP, Kreuzer P, Brunner S, Luchner A, Riegger GA, Endemann DH: Eplerenone prevents salt-induced vascular stiffness in Zucker diabetic fatty rats: a preliminary report. Cardiovasc Diabetol. 2011, 10: 94-10.1186/1475-2840-10-94. PubMedCentralCrossRefPubMed
Gómez-Marcos MA, Recio-Rodríguez JI, Patino-Alonso MC, Agudo-Conde C, Gómez-Sánchez L, Rodríguez-Sánchez E, Martín-Cantera C, García-Ortiz L: Relationship between intima-media thickness of the common carotid artery and arterial stiffness in subjects with and without type 2 diabetes: a case-series report. Cardiovasc Diabetol. 2011, 10: 3-10.1186/1475-2840-10-3. PubMedCentralCrossRefPubMed
Armentano RL, Levenson J, Barra JG, Fischer EI, Breitbart GJ, Pichel RH, Simon A: Assessment of elastin and collagen contribution to aortic elasticity in conscious dogs. Am J Physiol. 1991, 260: 1870-1877.
Shadwick RE: Mechanical design in arteries. J Exp Biol. 1999, 202: 3305-3313. PubMed
Serizawa K, Yogo K, Aizawa K, Tashiro Y, Ishizuka N: Nicorandil prevents endothelial dysfunction due to antioxidative effects via normalisation of NADPH oxidase and nitric oxide synthase in streptozotocin diabetic rats. Cardiovasc Diabetol. 2011, 10: 105-10.1186/1475-2840-10-105. PubMedCentralCrossRefPubMed
Wong MS, Delansorne R, Man RY, Svenningsen P, Vanhoutte PM: Chronic treatment with vitamin D lowers arterial blood pressure and reduces endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol. 2010, 299: 1226-1234. 10.1152/ajpheart.00288.2010. CrossRef
Dong Y, Stallmann-Jorgensen IS, Pollock NK, Harris RA, Keeton D, Huang Y, Li K, Bassali R, Guo DH, Thomas J, Pierce GL, White J, Holick MF, Zhu H: A 16-week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness. J Clin Endocrinol Metab. 2010, 95: 4584-4591. 10.1210/jc.2010-0606. CrossRefPubMed
- Effect of vitamin D on aortic remodeling in streptozotocin-induced diabetes
Alberto P Avolio
- BioMed Central
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