Relationship between arterial calcification and bone loss in a new combined model rat by ovariectomy and vitamin D(3)...

Epidemiological studies have reported an association between arterial calcification and bone loss after menopause. However, the underlying mechanism of the association remains unclear. Therefore, to explore the possible mechanisms of the association, we tried to develop a new combined model rat of ovariectomy (OVX, an animal model of osteoporosis) and vitamin D(3) plus nicotine (VDN rat, an animal model of arterial calcification). We tested them by using sham-operated control rats (SC), OVX control rats (OC), and OVX plus VDN-treated rats (OVN). Dissections were performed twice at 4 (4SC, 4OC, and 4OVN) and 8 (8SC, 8OC, and 8OVN) weeks after treatment. 8OVN showed bone loss and arterial calcification, although 8OC showed only bone loss. Moreover, arterial calcium content was associated with indexes of bone loss at 8 weeks. Thus, the OVN rat is considered a good model to examine the relationship of the two disorders after menopause. Additionally, the arterial endothelin-1 (ET-1, a potent regulator of arterial calcification) levels increased in both 4OVN and 8OVN, and the level was associated with arterial calcium content at 8 weeks. Furthermore, the arterial endothelial nitric oxide synthase (eNOS) protein, which is an enzyme that produces nitric oxide (an antiatherosclerotic substance), was significantly reduced in only 8OVN. Estrogens affect the alterations of the eNOS and ET-1 proteins. Therefore, we suggest that impairment of the ET-1- and NO-producing system in arterial tissue during periods of rapid bone loss by estrogen deficiency might be a mechanism of the relationship between the two disorders seen in postmenopausal women.