Maternal and postnatal vitamin D ingestion influences rat aortic structure, function and elastin content.
OBJECTIVE
Subtle impairment of fetal nutrition appears to predict hypertension and atherosclerosis in adults. It has been hypothesised that impaired aortic elastogenesis is the initiating step in adult hypertension and aortic aneurysms. Vitamin D has been shown to inhibit elastin synthesis by cultured smooth muscle cells. Here we have investigated, in rats, the hypothesis that increased exposure to vitamin D during gestation and in the postnatal period alters aortic elastin content and aortic function.


METHODS
Nine breeding pairs of Sprague-Dawley rats were allocated to one of three diets containing 3000 (control group), 6000 (low dose) or 12,000 (high dose) IU/kg vitamin D during pregnancy and lactation. Male pups were continued on the same diet until 6 weeks of age. Aortic elastin content was assessed by measuring desmosine+isodesmosine content using capillary zone electrophoresis. Transverse aortic sections were used for quantification of elastic lamellae and morphometric analysis. The contractility of aortic rings was assessed in an organ bath preparation.


RESULTS
The desmosine+isodesmosine content of the abdominal aorta of 6-week-old male pups, was 14.1, 10.0 and 10.1 nmol/mg dry weight in the control (n=20), low- (n=23) and high-dose (n=15) groups, respectively (P=0.007). The median number of elastic lamellae of the distal thoracic aorta was 8.25, 7.13 and 6.88 in the control, low-dose and high-dose groups, respectively (P<0.001). There were no significant differences in aortic cross-sectional areas or media:adventitia ratios. The mean peak tension of aortic rings, in response to phenylephrine, was 1.3 g, 1.12 g and 0.87 g in the control, low- and high-dose groups respectively (P=0.002).


CONCLUSIONS
In rats, exposure to increased amounts of vitamin D during gestation and early life results in a reduction of aortic elastin content, number of elastic lamellae in the aorta and force generation in aortic rings.
University Department of Surgery, Fremantle Hospital, P.O. Box 480, Western Australia 6959, Fremantle, Australia. pnorman@cyllene.uwa.edu.au
Paul
P
Norman
Ian
I
Moss
Minder
M
Sian
Martin
M
Gosling
Janet
J
Powell
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D003895:Desmosine / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D005260:Female; D007524:Isodesmosine / Q000032:analysis; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009924:Organ Culture Techniques; D010196:Pancreatic Elastase / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014807:Vitamin D / Q000494:pharmacology*
D003895:Desmosine; D014807:Vitamin D; D007524:Isodesmosine; D010196:Pancreatic Elastase