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(Hypertension. 1997;30:150-156.)
© 1997 American Heart Association, Inc.

Articles

Ultraviolet Light May Contribute to Geographic and Racial Blood Pressure Differences

Stephen G. Rostand

From the Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, The University of Alabama at Birmingham.

Correspondence to Stephen G. Rostand, MD, Division of Nephrology, 604 Zeigler Building, The University of Alabama at Birmingham, Birmingham, AL 35294.

	Abstract

Top Abstract Introduction UV Light and BP Race, PTH, Vitamin D,... Summary and Conclusions References

 
Abstract 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.

Key Words: parathyroid hormones • vitamin D • blood pressure • geography • race • ultraviolet rays

	Introduction

Top Abstract Introduction UV Light and BP Race, PTH, Vitamin D,... Summary and Conclusions References

 
Mean systolic and diastolic pressures and the prevalence of hypertension vary widely throughout the world. BP is higher and the occurrence of hypertension greater in more industrialized or Westernized regions (20% to 30%), whereas the opposite is found in the least industrialized regions (0% to 15%).^{1 2 3 4 5 6} Data also suggest that people of color living in the United States⁷ and Great Britain⁸ have more hypertension than those of European origin. Moreover, those living in their indigenous regions have lower mean BPs and frequencies of hypertension and rarely have the age-associated rise in BP seen often in whites and African Americans.^{3 4 9}

Explanations for these geographic and racial differences in BP and prevalence of hypertension have mostly been related to dietary changes, particularly sodium and potassium consumption^{1 10 11 12} ; to intrinsic racial differences in renal hemodynamics and sodium metabolism^{13 14 15 16} ; and to social and economic stresses of industrialization, or Westernization.^{4 17 18} However, other factors may be involved. Alterations in calcium, vitamin D, and PTH status have been observed in experimental^{19 20 21} and human^{22 23 24 25 26 27 28 29} hypertension, and although controversial,^{29 30} such changes have been felt to contribute to its pathogenesis. As will be discussed in more detail below, these findings, along with data from a variety of sources showing seasonal and geographic differences in BP, suggest that reduced epidermal vitamin D₃ photosynthesis caused by decrements in ambient UVB radiation at progressive distances from the equator results in reduced vitamin D stores and increased PTH secretion. This effect may be further accentuated by less efficient vitamin D₃ photosynthesis in deeply pigmented skin. Together, these conditions may not only contribute to geographic differences in BP but also may partially explain the greater prevalence of hypertension in dark-skinned people living in temperate climates.

	UV Light and BP

Top Abstract Introduction UV Light and BP Race, PTH, Vitamin D,... Summary and Conclusions References

 
In humans, ambient sunlight plays a major role in vitamin D production because high-energy UVB light enters the epidermis, transforming 7-dehydrocholesterol (provitamin D₃) to previtamin D₃,^{31 32} with subsequent conversion to the more stable vitamin D₃. Vitamin D₃ is translocated into the circulation and transported to the liver where it is converted to 25(OH)D₃, the major index of total body vitamin D₃ stores,^{31 32} before its final renal conversion to 1,25(OH)₂D₃. Among the numerous factors influencing cutaneous production of vitamin D₃ are seasonal changes, degree of skin pigmentation, and latitude north or south of the equator.^{31 33 34 35}

It has been observed that with each 10° distance from the equator, there is a progressive fall in ambient UVB radiation,³³ and BP rises at increasing distances from the equator. For example, when mean BPs noted for the various centers in the INTERSALT study are plotted in relation to their latitudes north or south of the equator, a highly significant positive association is seen (Fig 1).¹ The prevalence of hypertension has a similar relationship to latitude (Fig 2).¹ Moreover, had 95% predictive limits been used instead of confidence limits, the eightnon-INTERSALT centers^{36 37 38 39 40} (Fig 2, labeled open boxes) would be seen to fall well within these predictive intervals. There is also an association between mean BP and latitude for black men living in Nigeria, Barbados, and the United States.⁴¹ However, a comparison of BPs of Cape Verdeans and Cape Verde immigrants to New England showed only small differences.⁴²

View larger version (24K): [in this window] [in a new window]   Figure 1. A, Relationship of mean systolic blood pressure (SBP) and distance north or south of the equator. Symbols represent north or latitudes of INTERSALT Centers.3 B, Relationship of mean diastolic blood pressure (DBP) to distance north or south of the equator. For both figures, broken lines represent 95% confidence limits.

View larger version (24K): [in this window] [in a new window]   Figure 2. Relationship of prevalence of hypertension to distance north or south of the equator. Labeled open boxes represent non-INTERSALT centers36 37 38 39 40 ; solid boxes are INTERSALT centers. Broken lines represent 95% confidence limits. Regression line and confidence limits are derived from INTERSALT centers only.

Seasonal variations in BP also have been observed in temperate climates,^{43 44} with BP highest in winter, when ambient UVB radiation is least, and at a nadir in summer, during peak UVB light. Although one study⁴³ related seasonal changes in BP to ambient temperature, another⁴⁴ was more cautious in its interpretation. Thus, it is possible that seasonal and geographic changes in BP are inversely associated with ambient UVB light intensity and with vitamin D stores producing increased PTH secretion. Support for this viewpoint comes from two studies examining the direct effects of UVB light on BP. Kokot et al⁴⁵ found small reductions in BP in 23 Polish subjects exposed to light of UVB wavelengths. Similarly, Krause et al⁴⁶ recently reported that BP and PTH fell after UVB irradiation of eight hemodialysis patients. This was associated with increases in 25(OH)D₃ and 1,25(OH)₂D₃, unlike Kokot et al, who found no changes in vitamin D metabolites from their elevated baselines.

	Race, PTH, Vitamin D, and BP

Top Abstract Introduction UV Light and BP Race, PTH, Vitamin D,... Summary and Conclusions References

 
Hyperparathyroidism is the most consistent change in calcium/vitamin D/PTH status in human hypertension.^{24 25 27 47} Increased plasma PTH and 1,25(OH)₂D₃ have been found in low-renin and other forms of hypertension^{24 26 27} ; in hypertensive individuals after salt loading^{48 49 50} ; in African Americans, who also have been reported to have reduced plasma 25(OH)D₃ concentrations and increased parathyroid mass^{51 52} ; and in Zairians living in Europe compared with those living in Zaire.⁵³ Although no large-scale systematic studies of geographic differences in vitamin D metabolites have been conducted, one study of Europeans living between 35°N and 60°N showed small increases in vitamin D stores at more northern latitudes.⁵⁴ Nevertheless, these observations, although controversial and derived from various sources, when taken together suggest an effect of UV radiation on BP, possibly mediated through changes in vitamin D stores and PTH secretion.

Geographic variations in UV light, BP, PTH, and perhaps vitamin D stores discussed above may be further accentuated by seasonal changes. The least UVB radiation is available in winter and the most in summer^{33 34} ; this may account for wintertime reductions of 25(OH)D₃ in temperate climates.^{34 55 56 57 58} For example, in winter, at 42°N and 52°N, skin samples exposed to midday sunlight produced no previtamin D₃, but at 18°N and 34°N, previtamin D₃ was formed.³⁴ However, in the latter case, whether sunlight was sufficient to maintain adequate vitamin D stores is uncertain since wintertime reductions of "antirachitic factors" have been observed at 18°N.⁵⁹ In winter, PTH increases correspondingly.^{57 58} Since animal studies show that decreases in 25(OH)D₃ cause transient reductions in 1,25(OH)₂D₃,^{60 61} it is possible that the wintertime fall in 25(OH)D₃ results in decreases in 1,25(OH)₂D₃ that stimulate PTH secretion. Increased PTH secretion can augment 1,25(OH)D₃ production,^{31 57 61 62} which may in part explain the paradoxically normal serum 1,25(OH)₂D₃ levels seen with reduced vitamin D stores^{31 32 57} and the elevated concentrations observed in some American and European blacks.^{52 53}

The above observations may have important implications for the BP of dark-skinned people because the degree of skin pigmentation also alters the effectiveness of vitamin D₃ photosynthesis. Also, it has been reported that within the African American community, greater skin pigmentation, measured by UVB light reflectance, is associated with higher BP.^{63 64 65} Holick³¹ reported that 20% to 30% of UVB radiation is transmitted through the epidermis of white skin, but penetration is less than 5% in deeply pigmented skin of African Americans. When skin specimens were exposed to simulated sunlight under identical conditions, black skin required a longer exposure than white skin to maximize previtamin D production.³¹ Also, black subjects required whole-body UVB radiation six times that of whites (enough to cause severe second-degree sunburn in whites) to produce a similar increase in circulating blood levels of 25(OH)D₃.³¹ Such observations are not limited to people of African origin. Studies of Pakistani and Indian children living in the United States suggest that their capacity to produce vitamin D is the same as whites, but like blacks, they require longer exposure to UV light because of increased skin melanin content.³¹ Thus, a reduced efficiency of vitamin D₃ photosynthesis may partially explain some of the interracial and intraracial differences in vitamin D metabolites and PTH concentrations and the apparent direct association between BP level and the degree of skin pigmentation in African Americans.^{63 64 65}

Although thus far a relationship of epidermal vitamin D₃ photosynthesis to BP has been emphasized, vitamin D, PTH, and BP interactions may also be linked to reduced concentrations of serum ionized calcium noted in experimental hypertension and especially in low-renin human hypertension.^{22 27} It has been suggested that these changes in serum ionized calcium and PTH secretion are caused by calciuresis either resulting from a primary renal calcium leak or secondary to increased renal sodium excretion,^{66 67 68} but increased urinary calcium excretion has not been found in all subjects.^{27 47 68 69} However, these differences may be due to the absence of a standardized dietary calcium intake in several of the negative studies.⁶⁸

Alternatively, changes in calcium homeostasis could relate to decreased dietary calcium intake and/or calcium entry. In animal models, particularly the spontaneously hypertensive rat, intestinal calcium malabsorption and altered cellular calcium transport have been demonstrated,^{20 70 71 72} but in human hypertension, no disturbances of intestinal calcium absorption have been noted.⁷³ Nevertheless, a high prevalence of milk intolerance, particularly in blacks, due to either lactase deficiency⁷⁴ or other factors⁷⁵ might lead to voluntary avoidance of milk products or to reduced calcium absorption consequent to rapid gastrointestinal transit times. Decreased calcium absorption might also be due to dietary intake of food rich in phytates that can bind calcium. Reduced calcium entry can lead to decreased concentrations of 25(OH)D₃. Both low serum ionized calcium and 25(OH)D₃ stimulate PTH production.⁶¹ Low 25(OH)D₃ plasma concentrations can cause decreases in 1,25(OH)₂D₃, with subsequent augmentation of PTH secretion. This will in turn stimulate 25(OH)D₃ 1-hydroxylase activity to correct 1,25(OH)₂D₃ concentrations.^{60 62 76} Calcium depletion not only augments PTH secretion, it also has been shown to increase BP in experimental hypertension.^{77 78} Moreover, reduced dietary calcium has been demonstrated in some studies of human hypertension^{79 80} ; however, there is no agreement on its prevalence.^{23 30} Nevertheless, calcium supplementation has been shown to lower BP in experimental hypertension^{81 82 83} and in human hypertensive subjects.^{84 85}

It has been reported that African Americans consume less calcium than whites,⁷⁹ perhaps because of voluntary avoidance of milk products, for reasons mentioned above, but the evidence is not strong. Only one phase of the National Health and Nutrition Examination Surveys (NHANES) revealed an association between low calcium intake and BP in African Americans⁸⁶ ; another study showed no racial differences in calcium intake.⁵³ However, as suggested above, an absence of racial differences in calcium intake might not accurately indicate intergroup rates or degrees of calcium entry into the circulation. Thus, it may be that in blacks, reduced calcium entry contributes to their susceptibility to hypertension, particularly in the presence of inefficient epidermal photosynthesis of vitamin D₃.

The mechanisms whereby changes in calcium/vitamin D/PTH status affect BP and their relative contributions are uncertain. Intracellular calcium concentration is elevated in erythrocytes and platelets of most, but not all, patients with essential hypertension.^{28 87 88 89} These changes are thought to be related to transcellular sodium and calcium fluxes due to increased sodium loads^{48 49 66} or to abnormal plasma PTH and/or 1,25(OH)₂D₃ concentrations^{87 90 91} and may in part mediate increased vascular smooth muscle tone. 1,25(OH)₂D₃ has been shown to enhance the contractile properties of resistance vessels in animal models by affecting intracellular calcium and by altering adrenergic responsiveness.^{91 92 93 94 95} PTH may interact with the vascular endothelium.^{96 97 98} At present, however, there is no agreement that all hypertensive individuals have altered vitamin D status^{69 99 100} or that Africans living in America or elsewhere have increased intracellular calcium concentrations.^{89 101 102 103} However, low-renin hypertension occurs frequently in African Americans, and increased intracellular calcium is found more often in this condition,^{26 27 28} suggesting that increased intracellular calcium might mediate BP control in this population.

Alterations in vitamin D and PTH status can affect vascular growth and structure. Vitamin D₃ depletion has been associated with increased myocardial collagen content,¹⁰⁴ and high calcium diets can prevent intramyocardial vascular wall thickening,¹⁰⁵ suggesting that in some tissues, cell growth is modified by changes in PTH and vitamin D concentrations. In this regard, a recent study showed that PTH had a permissive effect in the genesis of vessel wall thickening,¹⁰⁶ and another observed that 1,25(OH)₂D₃ stimulated proliferation of quiescent vascular smooth muscles in culture,¹⁰⁷ suggesting a possible role for this hormone in vascular smooth muscle cell proliferation.

	Summary and Conclusions

Top Abstract Introduction UV Light and BP Race, PTH, Vitamin D,... Summary and Conclusions References

 
An hypothesis is summarized in Fig 3 which suggests that reduced photosynthesis of vitamin D₃ at increasing distances from the equator, in deeply pigmented peoples, and with reduction of skin surface exposure produces limited vitamin D stores, resulting in augmented PTH production. There may be an additional effect of reduced dietary calcium intake or absorption in some people. Increased PTH secretion and, in some circumstances, increased 1,25(OH)₂D₃ concentrations may in turn affect vascular structure and function, thus influencing BP in blacks and in others living at distances from the equator. The hypothesis attempts to integrate numerous clinical and experimental observations regarding vitamin D, calcium, and PTH gathered from many disciplines in order to gain further understanding of the geographical differences in BP and of the susceptibility of African Americans to developing hypertension. As in any synthesis of this type, there are many pitfalls. Numerous studies of seasonal or geographic BP differences were not accompanied by measurements of PTH or vitamin D metabolites and the converse. In fact, geographic differences in vitamin D metabolites have not been well described, and the available data seem contradictory. Others found opposite or no changes in vitamin D metabolites and did not categorize the hypertension studied.^{69 99 100} Much of the variability in PTH and vitamin D metabolite concentrations occurred because physiological conditions and assay methodologies differed among studies. In many, seasonal conditions, sunlight exposure, dietary calcium, phosphorus, and vitamin D, or other factors influencing bone, calcium, vitamin D, and PTH concentrations were not reported. Many studies did not specify the ethnic background of the patients. In addition, since most industrialized nations are distant from the equator, cross-cultural conflicts and the social, economic, and psychological stress related to them may be important contributors to the BP differences discussed here.

View larger version (25K): [in this window] [in a new window]   Figure 3. Outline of proposed interrelationships between BP regulation and UV light, vitamin D, PTH, and calcium metabolism. Solid arrows are interactions established in humans. Stippled arrows are interactions established in animal and in vitro studies. Stimulatory and inhibitory effects are denoted by plus and minus signs, respectively.

Despite such pitfalls, the evidence presented suggests a role for altered PTH and calcium status consequent to reduced skin photosynthesis of vitamin D₃ in geographic and racial differences in BP. The proposed hypothesis does not detract from other proposed mechanisms of hypertension and fits well with a role of sodium in hypertension, since the strongest associations between alterations of PTH, vitamin D, and calcium status have been noted in low-renin, presumably volume-expanded, forms of hypertension. The coexistence of less-efficient vitamin D₃ photosynthesis in deeply pigmented skin, reductions in renal sodium excretion rates, and salt sensitivity^{11 16} in African Americans complements an hypothesis proposing that African slave trade with the Americas abruptly exposed a population uniquely adapted to low salt, high potassium diets of West Africa to nontraditional European diets high in sodium and low in potassium, causing attendant increases in BP.¹⁰⁸ Explanations for the evolutionary advantages of highly pigmented skin have been discussed without conclusion.^{109 110} Nevertheless, the migration away from equatorial regions of salt-sensitive, dark-skinned populations also well adapted to high UV light conditions may have had an additional impact on BP by reducing ambient UV light, thus affecting calcium, PTH, and vitamin D status and in turn BP. This hypothesis warrants further investigation and could be tested by exposing salt-sensitive, low-renin hypertensive Europeans and Africans to varying doses of UV light or perhaps more easily by supplementing them orally with vitamin D.

	Selected Abbreviations and Acronyms

 

BP = blood pressure 1,25(OH)2D3 = 1,25-dihydroxyvitamin D3 25(OH)D3 = 25-hydroxyvitamin D3 PTH = parathyroid hormone UVB = ultraviolet light, midrange sunbeam spectrum

	Acknowledgments

 
This work was in part supported by the Nephrology Research and Training Center, Division of Nephrology, The University of Alabama at Birmingham and a grant from the National Institutes of Health (NIDDK 1 UO1 DK 48669). I would like to thank Drs Tilman Drüeke, David Warnock, Murray Epstein, and Katherine Rostand for their helpful comments, suggestions, and encouragement and the entire faculty and staff of INSERM Unité 90, Hôpital Necker, Paris, France, for their kind hospitality, support, and patience during my sabbatical. Katharine A. Kirk, PhD, performed the statistical analyses.

Received September 30, 1996; first decision October 25, 1996; accepted January 24, 1997.

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