Effect of vitamin D on aortic remodeling in streptozotocin-induced diabetes.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Cardiology, University of Tartu, 8 Puusepa Street, Tartu, 51014, Estonia. erik.salum@gmail.com
Erik
E
Salum
Priit
P
Kampus
Mihkel
M
Zilmer
Jaan
J
Eha
Mark
M
Butlin
Alberto P
AP
Avolio
Taavi
T
Põdramägi
Andres
A
Arend
Marina
M
Aunapuu
Jaak
J
Kals
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001018:Aortic Diseases / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D019587:Dietary Supplements; D004547:Elastic Tissue / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004548:Elasticity; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D011673:Pulsatile Flow / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
D015415:Biomarkers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D014807:Vitamin D; D002762:Cholecalciferol; D013311:Streptozocin; C018524:N,N-dimethylarginine; D001120:Arginine; C104450:25-hydroxyvitamin D