Ultraviolet Light May Contribute to Geographic and Racial Blood Pressure Differences

[Guest guest]

Want to lower your blood pressure. Just move closer to the equator or get a

sun tan…or both. How about Vitamin D? Maybe we shouldn’t worry about it.

Just give thanks. Don’t worry. Be happy.

 

 

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

 

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

 

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%). <http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R1#R1>

1 <http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R2#R2> 2

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R3#R3> 3

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R4#R4> 4

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R5#R5> 5

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R6#R6> 6 Data

also suggest that people of color living in the United States

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R7#R7> 7 and

Great Britain

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R8#R8> 8 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R3#R3> 3

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R4#R4> 4

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R9#R9> 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

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R1#R1> 1

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R10#R10> 10

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R11#R11> 11

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R12#R12> 12 ; to

intrinsic racial differences in renal hemodynamics and sodium metabolism

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R13#R13> 13

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R14#R14> 14

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R15#R15> 15

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R16#R16> 16 ;

and to social and economic stresses of industrialization, or Westernization.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R4#R4> 4

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R17#R17> 17

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R18#R18> 18

However, other factors may be involved. Alterations in calcium, vitamin D,

and PTH status have been observed in experimental

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R19#R19> 19

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R20#R20> 20

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R21#R21> 21 and

human <http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R22#R22>

22 <http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R23#R23> 23

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R24#R24> 24

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R25#R25> 25

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R26#R26> 26

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R27#R27> 27

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R28#R28> 28

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R29#R29> 29

hypertension, and although controversial,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R29#R29> 29

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R30#R30> 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

 

 

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,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R31#R31> 31

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R32#R32> 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,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R31#R31> 31

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R32#R32> 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R31#R31> 31

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R33#R33> 33

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R34#R34> 34

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R35#R35> 35

 

It has been observed that with each 10° distance from the equator, there is

a progressive fall in ambient UVB radiation,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R33#R33> 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

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#F1#F1> ).

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R1#R1> 1 The

prevalence of hypertension has a similar relationship to latitude (Fig 2

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#F2#F2> ).

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R1#R1> 1

Moreover, had 95% predictive limits been used instead of confidence limits,

the eightnon-INTERSALT centers

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R36#R36> 36

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R37#R37> 37

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R38#R38> 38

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R39#R39> 39

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R40#R40> 40 (Fig

2 <http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#F2#F2> ,

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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R41#R41> 41

However, a comparison of BPs of Cape Verdeans and Cape Verde immigrants to

New England showed only small differences.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R42#R42> 42

 

Seasonal variations in BP also have been observed in temperate climates,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R43#R43> 43

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R44#R44> 44 with

BP highest in winter, when ambient UVB radiation is least, and at a nadir in

summer, during peak UVB light. Although one study

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R43#R43> 43

related seasonal changes in BP to ambient temperature, another

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R44#R44> 44 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 al

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R45#R45> 45

found small reductions in BP in 23 Polish subjects exposed to light of UVB

wavelengths. Similarly, Krause et al

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R46#R46> 46

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

 

Hyperparathyroidism is the most consistent change in calcium/vitamin D/PTH

status in human hypertension.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R24#R24> 24

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R25#R25> 25

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R27#R27> 27

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R47#R47> 47

Increased plasma PTH and 1,25(OH)2D3 have been found in low-renin and other

forms of hypertension

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R24#R24> 24

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R26#R26> 26

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R27#R27> 27 ; in

hypertensive individuals after salt loading

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R48#R48> 48

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R49#R49> 49

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R50#R50> 50 ; in

African Americans, who also have been reported to have reduced plasma

25(OH)D3 concentrations and increased parathyroid mass

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R51#R51> 51

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R52#R52> 52 ;

and in Zairians living in Europe compared with those living in Zaire.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R53#R53> 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R54#R54> 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

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R33#R33> 33

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R34#R34> 34 ;

this may account for wintertime reductions of 25(OH)D3 in temperate

climates.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R34#R34> 34

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R55#R55> 55

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R56#R56> 56

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R57#R57> 57

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R58#R58> 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. <http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R34#R34>

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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R59#R59> 59 In

winter, PTH increases correspondingly.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R57#R57> 57

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R58#R58> 58

Since animal studies show that decreases in 25(OH)D3 cause transient

reductions in 1,25(OH)2D3,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R60#R60> 60

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R61#R61> 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,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R31#R31> 31

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R57#R57> 57

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R61#R61> 61

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R62#R62> 62

which may in part explain the paradoxically normal serum 1,25(OH)2D3 levels

seen with reduced vitamin D stores

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R31#R31> 31

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R32#R32> 32

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R57#R57> 57 and

the elevated concentrations observed in some American and European blacks.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R52#R52> 52

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R53#R53> 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R63#R63> 63

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R64#R64> 64

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R65#R65> 65

Holick <http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R31#R31>

31 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R31#R31> 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R31#R31> 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R31#R31> 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R63#R63> 63

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R64#R64> 64

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R65#R65> 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R22#R22> 22

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R27#R27> 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,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R66#R66> 66

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R67#R67> 67

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R68#R68> 68 but

increased urinary calcium excretion has not been found in all subjects.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R27#R27> 27

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R47#R47> 47

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R68#R68> 68

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R69#R69> 69

However, these differences may be due to the absence of a standardized

dietary calcium intake in several of the negative studies.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R68#R68> 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,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R20#R20> 20

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R70#R70> 70

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R71#R71> 71

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R72#R72> 72 but

in human hypertension, no disturbances of intestinal calcium absorption have

been noted.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R73#R73> 73

Nevertheless, a high prevalence of milk intolerance, particularly in blacks,

due to either lactase deficiency

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R74#R74> 74 or

other factors

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R75#R75> 75

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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R61#R61> 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{alpha}-hydroxylase activity to correct 1,25(OH)2D3

concentrations.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R60#R60> 60

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R62#R62> 62

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R76#R76> 76

Calcium depletion not only augments PTH secretion, it also has been shown to

increase BP in experimental hypertension.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R77#R77> 77

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R78#R78> 78

Moreover, reduced dietary calcium has been demonstrated in some studies of

human hypertension

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R79#R79> 79

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R80#R80> 80 ;

however, there is no agreement on its prevalence.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R23#R23> 23

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R30#R30> 30

Nevertheless, calcium supplementation has been shown to lower BP in

experimental hypertension

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R81#R81> 81

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R82#R82> 82

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R83#R83> 83 and

in human hypertensive subjects.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R84#R84> 84

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R85#R85> 85

 

It has been reported that African Americans consume less calcium than

whites, <http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R79#R79>

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 Americans

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R86#R86> 86 ;

another study showed no racial differences in calcium intake.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R53#R53> 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R28#R28> 28

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R87#R87> 87

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R88#R88> 88

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R89#R89> 89

These changes are thought to be related to transcellular sodium and calcium

fluxes due to increased sodium loads

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R48#R48> 48

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R49#R49> 49

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R66#R66> 66 or

to abnormal plasma PTH and/or 1,25(OH)2D3 concentrations

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R87#R87> 87

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R90#R90> 90

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R91#R91> 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R91#R91> 91

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R92#R92> 92

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R93#R93> 93

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R94#R94> 94

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R95#R95> 95 PTH

may interact with the vascular endothelium.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R96#R96> 96

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R97#R97> 97

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R98#R98> 98 At

present, however, there is no agreement that all hypertensive individuals

have altered vitamin D status

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R69#R69> 69

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R99#R99> 99

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R100#R100> 100

or that Africans living in America or elsewhere have increased intracellular

calcium concentrations.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R89#R89> 89

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R101#R101> 101

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R102#R102> 102

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R103#R103> 103

However, low-renin hypertension occurs frequently in African Americans, and

increased intracellular calcium is found more often in this condition,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R26#R26> 26

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R27#R27> 27

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R28#R28> 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,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R104#R104> 104

and high calcium diets can prevent intramyocardial vascular wall thickening,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R105#R105> 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,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R106#R106> 106

and another observed that 1,25(OH)2D3 stimulated proliferation of quiescent

vascular smooth muscles in culture,

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R107#R107> 107

suggesting a possible role for this hormone in vascular smooth muscle cell

proliferation.

 

Summary and Conclusions

 

An hypothesis is summarized in Fig 3

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#F3#F3> 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.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R69#R69> 69

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R99#R99> 99

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R100#R100> 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.

 

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

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R11#R11> 11

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R16#R16> 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. <http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R108#R108>

108 Explanations for the evolutionary advantages of highly pigmented skin

have been discussed without conclusion.

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R109#R109> 109

<http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf#R110#R110> 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.

 

http://hyper.ahajournals.org/cgi/content/full/30/2/150?eaf