title: Both high and low plasma levels of 25-hydroxy vitamin D increase blood pressure in a normal rat model.
abstract: The lower threshold plasma 25-hydroxy vitamin D (25(OH)D) level for optimal cardiovascular health is unclear, whereas the toxicity threshold is less clear. The aim of this study was to examine the cardiovascular-vitamin D dose-response curve in a normal rat model. Doses of cholecalciferol ranged from deficiency to toxic levels (equivalent to human doses of 0, 0·015, 0·25 and 3·75mg/d) for 4 weeks, and then cardiovascular health was examined using blood pressure telemetry and high-resolution ultrasound in normal male rats (n 16/group, 64 rats total). After 1 month, only the 0·25mg/d group had plasma 25(OH)D that was within current recommended range (100-125 nmol/l), and all groups failed to change plasma Ca or phosphate. Systolic blood pressure increased significantly (10-15 mmHg) in the rat groups with plasma 25(OH)D levels at both 30 and 561 nmol/l (groups fed 0 and 3·75mg/d) compared with the group fed the equivalent to 0·015mg/d (43 nmol/l 25(OH)D). Although not significant, the group fed the equivalent to 0·25mg/d (108 nmol/l 25(OH)D) also showed a 10 mmHg increase in systolic blood pressure. Carotid artery diameter was significantly smaller and wall thickness was larger, leading to higher peak carotid systolic blood velocity in these two groups. Despite these vascular changes, cardiac function did not differ among treatment groups. The key finding in this study is that arterial stiffness and systolic blood pressure both showed a U-shaped dose-response for vitamin D, with lowest values (best cardiovascular health) observed when plasma 25(OH)D levels were 43 nmol/l in normal male rats.
authors.affiliation: 1Veterinary Biomedical Sciences,University of Saskatchewan,52 Campus Drive,Saskatoon,SK,Canada,S7N 5B4.
authors.forename: Naghmeh Z
authors.initials: NZ
authors.lastname: Mirhosseini
authors.affiliation: 2Toxicology Graduate Program,University of Saskatchewan,51 Campus Drive,Saskatoon,SK,Canada,S7N 5B3.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Knaus
authors.affiliation: 1Veterinary Biomedical Sciences,University of Saskatchewan,52 Campus Drive,Saskatoon,SK,Canada,S7N 5B4.
authors.forename: Kaylee
authors.initials: K
authors.lastname: Bohaychuk
authors.affiliation: 1Veterinary Biomedical Sciences,University of Saskatchewan,52 Campus Drive,Saskatoon,SK,Canada,S7N 5B4.
authors.forename: Jaswant
authors.initials: J
authors.lastname: Singh
authors.affiliation: 3Pharmacy and Nutrition,University of Saskatchewan,104 Clinic Place,Saskatoon,SK,Canada,S7N 2Z4.
authors.forename: Hassan A
authors.initials: HA
authors.lastname: Vatanparast
authors.affiliation: 1Veterinary Biomedical Sciences,University of Saskatchewan,52 Campus Drive,Saskatoon,SK,Canada,S7N 5B4.
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Weber
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002112:Calcifediol / Q000097:blood*; D002118:Calcium / Q000097:blood; D002302:Cardiac Output; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology; D002762:Cholecalciferol / Q000008:administration & dosage / Q000506:poisoning* / Q000627:therapeutic use; D014676:Diet, Vegetarian / Q000009:adverse effects; D004195:Disease Models, Animal; D004452:Echocardiography; D006321:Heart / Q000000981:diagnostic imaging / Q000503:physiopathology; D006973:Hypertension / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D010710:Phosphates / Q000097:blood; D017208:Rats, Wistar; D013318:Stroke Volume; D013997:Time Factors; D018608:Ultrasonography, Doppler; D059289:Vascular Stiffness; D014808:Vitamin D Deficiency / Q000097:blood / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D010710:Phosphates; D002762:Cholecalciferol; D002112:Calcifediol; D002118:Calcium
keywords:  25(OH)D 25-hydroxy vitamin D;  NOAEL no observed adverse effects level;  RAAS renin–angiotensin–aldosterone system; Arterial stiffness; Hypertension; Toxic levels; Vitamin D; Vitamin D deficiency