Parathyroid hormone, vitamin D, and cardiovascular disease in chronic renal failure

Non-trauma mortality in elderly women with low bone mineral density

Mean systolic and diastolic pressures and the prevalence of hypertension vary throughout the world Published data suggest a linear rise in blood pressure at increasing distances from the equator Similarly, blood pressure is higher in winter than summer Blood pressure also is affected by variations in skin pigmentation Altered calcium, vitamin D, and parathyroid hormone status is associated with hypertension and may vary with latitude and season Since changes in UV light affect vitamin D and parathyroid hormone status and UV light intensity are influenced by seasonal change and latitude, these disparate observations suggest an association between blood pressure and ultraviolet light This discussion presents the hypothesis that reduced epidermal vitamin D3 photosynthesis associated with high skin melanin content and/or decreased UV light intensity at distances from the equator, alone or when coupled with decreased dietary calcium and vitamin D, may be associated with reduced vitamin D stores and increased parathyroid hormone secretion These changes may stimulate growth of vascular smooth muscle and enhance its contractility by affecting intracellular calcium, adrenergic responsiveness, and/or endothelial function Thus, UV light intensity and efficiency of epidermal vitamin D3 photosynthesis may contribute to geographic and racial variability in blood pressure and the prevalence of hypertension

Ultraviolet Light May Contribute to Geographic and Racial Blood Pressure Differences

Vitamin D deficiency is common and is primarily caused by a lack of ultraviolet-B (UVB) radiation from reduced sun exposure, and the consequent limiting of vitamin D production in the skin. The vitamin D endocrine system regulates about 3% of the human genome. Observational data support the concept that vitamin D is involved in the pathogenesis of cardiovascular diseases and arterial hypertension. The antihypertensive properties of vitamin D include renoprotective effects, suppression of the renin-angiotensin-aldosterone system, direct effects on vascular cells, and effects on calcium metabolism, including prevention of secondary hyperparathyroidism. The results of clinical studies largely, but not consistently, favor the hypothesis that vitamin D sufficiency promotes lowering of arterial blood pressure. Randomized, placebo-controlled trials are greatly needed to clarify and definitively prove the effect of vitamin D on blood pressure. In general, the antihypertensive effects of vitamin D seem to be particularly prominent in vitamin-D-deficient patients with elevated blood pressure. Thus, in view of the relatively safe and inexpensive way in which vitamin D can be supplemented, we believe that vitamin D supplementation should be prescribed to patients with hypertension and 25-hydroxyvitamin D levels below target values.

Vitamin D status and arterial hypertension: a systematic review

This study tests the hypothesis that reduced blood flow to the lower extremities may affect bone remodeling, resulting in a decrease in bone mineral density (BMD). BMD was measured in the axial and appendicular skeleton of 1292 elderly women (mean age, 71 years) enrolled in the Study of Osteoporotic Fractures. The ratio of the posterior tibial and brachial systolic blood pressures, the ankle/arm index, was used as a measure of blood flow to the legs. In the cross-sectional analysis, this index was positively correlated with BMD at the radius, calcaneus, and hip, but not at the spine. A decrease in the index of 2 standard deviations (SD) (as might occur in patients with moderate arterial disease) was associated with a decrease of 3.7% (95% CI, 1.7%, 5.8%) in hip BMD. The effect size at the hip decreased from 3.7 to 1.8% (and was not statistically significant) when adjustment was made for smoking and/or body mass index (BMI). In the prospective analysis, the rate of bone loss at the hip and calcaneus was greater (p < 0.05) among women whose annual decrease in ankle/arm index was more than 1 SD greater than the mean decrease. This increase was independent of estrogen use, smoking, BMI, pattern of fat distribution, history of diabetes, exercise, and ability to walk. The results from this prospective community-based study provide the first evidence that among relatively healthy older women decreased vascular flow in the lower extremities may be associated with an increased rate of bone loss at the hip and calcaneus.

Bone Mineral Density and Blood Flow to the Lower Extremities: The Study of Osteoporotic Fractures

The hypothesis that 1,25-dihydroxyvitamin D3 [1,25-(OH)2 vitamin D3] modulates vascular smooth muscle contractile function was tested. 1,25-(OH)2 vitamin D3 (50 ng/day) was administered by intraperitoneal injection over a 3-day period to 13-15-week-old male spontaneously hypertensive and Wistar-Kyoto normotensive rats. On the fourth day, serum was prepared and contractile force generation of isolated mesenteric resistance arteries was examined. Treatment with 1,25-(OH)2 vitamin D3 approximately doubled serum levels of the hormone and increased ionized and total serum Ca2+ and phosphate by 5-10%. No effect on blood pressure was detected. 1,25-(OH)2 vitamin D3 injection in both strains enhanced maximal stress generation to norepinephrine and serotonin by 30-40%, with no effect on apparent sensitivity of the vessels to the agonists. To assess the effect of a maneuver that elevates serum ionized Ca2+ without the addition of exogenous hormone, maximal stress generation was examined in resistance arteries isolated from rats fed diets containing 0.5% or 2% calcium over a 6-7-week period. Maximal stress generation in response to norepinephrine was greater in vessels from rats of both strains maintained on 0.5% calcium. It is concluded that 72-hour in vivo treatment with 1,25-(OH)2 vitamin D3 increases contractile force-generating capacity of resistance arteries without affecting blood pressure. It is proposed that this action of 1,25-(OH)2 vitamin D3 is the result of a direct action of the hormone on the vascular wall.

D W Wagman

Papers

Injection of 1,25-(OH)2 vitamin D3 enhances resistance artery contractile properties.