|Year : 1999 | Volume
| Issue : 3 | Page : 257-266
|Blood Vessel Structure in Hypertension
R John Irving, Brian R Walker
Department of Medical Sciences, University of Edinburgh, Western General Hospital, Crewe Road South Edinburgh, Scotland, United Kingdom
Click here for correspondence address and email
|How to cite this article:|
Irving R J, Walker BR. Blood Vessel Structure in Hypertension. Saudi J Kidney Dis Transpl 1999;10:257-66
The vascular tree is a supremely efficient mechanical system. It takes a lifetime for the subtle increase in work required of the vasculature in hypertension to manifest itself in the catastrophic events of stroke or myocardial infarction. A myriad of physiological, hormonal and pathological abnormalities have been observed in established hypertension. This review discusses the role of alterations in the structure of blood vessels in patients with essential hypertension, with particular reference to the specialized and regulatory vasculature of the kidney. These changes will be discussed in the context of hypertension as a lifelong process with origins in fetal life.
Increased peripheral resistance with a normal cardiac output is the hallmark of hypertension. Resistance varies throughout the vascular tree and vessels of less than 500 micrometers in diameter form the greatest component. , Abnormalities of these vessels have been described in hypertension in human skin,  muscle , conjunctival,  retinal [,8] and gut vasculature  and could be shown to increase resistance.  However, in the presence of normal renal function, the effect on blood pressure from increased peripheral resistance would be nullified by pressure natriuresis.  In other words, over a remarkably wide range of blood pressure, any rise in pressure is followed by increased sodium excretion, which restores the original blood pressure. Transplantation experiments performed in immunologic ally compatible rats, between hypertensive and normotensive individuals show that the transplanted kidney dictates the blood pressure of the recipient. , A series of patients with end-stage renal failure, as a result of severe hypertension, who had therapeutic renal transplantation, gained remission from hypertensive disease maintained over five years. 
This study preceded routine cyclosporin use, which confers hypertension upon most recipients. Therefore, if increased peripheral vascular resistance is a primary change in hypertension, factors involved in the generation and maintenance of increased vascular resistance must be considered for both renal and non-renal vasculature.
| Structural Changes in Peripheral Vessels|| |
The vasculature of an individual with established hypertension has several distortions from normal. Vessel walls are thickened in the small arteries and resistant arterioles. Moreover, vessels are diminished in number or rarefied. These changes have been described for more than one hundred years.
Thickening of vessel walls with consequent increase in wall to lumen ratio is called hypertrophy. Schiffrin has reviewed the methods used to investigate this change in humans.  The term implies growth and division of wall components but this may be misleading. Baumbach and Heistad  were the first to suggest that it is remodeling of existing vessel components that result in the thicker wall. They demonstrated this in cerebral arteries of Stroke prone Spontaneously Hypertensive Rats (SpSHR). Work reviewed by Heagerty et al  has shown that in most studies this is the dominant effect in essential hypertensive patients and in Spontaneously Hypertensive Rats (SHR). Growth and cell division contribute much less.
Rarefaction refers to reduced vessel number per volume of tissue. This phenomenon has been demonstrated in multiple tissues in humans and rats. Short described arteriolar rarefaction in hypertensive cadavers in the 1950s. ,. In vivo rarefaction has been demonstrated, in association with hypertension, in conjunctivae,  skeletal muscle4 and nail beds.  This may be a response to local pressure in the studied network and a functional state may precede anatomical changes. SHR have diminished numbers of arterioles, which can be overcome by high dose vasodilators in young animals but not in older animals.  However, this interpretation is challenged by data from experiments9 inducing hyper-tension by coarctation.  The hindquarters of the animal are not exposed to the elevated systemic pressure but nevertheless rarefaction occurs. The cellular mechanism involved in development of rarefaction may well involve apoptosis. Electron micrographic studies demonstrated cellular markers of apoptosis  in endothelial tissues in Goldblatt hypertensive rats (one kidney, one clip).
| Hemodynamic Effect of Structural Vascular Changes|| |
Bjorn Folkow in Sweden performed the key experiments that first illustrated the functional significance of these changes in the 1950s. Prior to this, decreases in the minimum vascular resistance of tissues had been described in hypertensive patients with plethysmography.  Folkow showed for the first time  that the relationship between minimum vascular resistance and presser responses to noradrcnaline was identical in hypertensives and normatensives. He inferred that for any given presser tone, resistance from hypertensive vessels would be greater as a result of the increased luminal encroachment by the thickened wall. Thus, the structural change in the vessel wall is translated into the functional change of increased resistance without requiring alterations in smooth muscle activity or pharmacological sensitivity to vasoactive agents
The "Structural Factor" Folkow described is a generally accepted principle in hypertension. The relative significance of rarefaction arouses more controversy. Hallback et al . simulated rarefaction in the hindquarters of a rat by injection of microspheres. These were 50 pm in diameter and blocked 50% of microvessels of that size. No enhancement of the effect of vasoconstrictors was observed and he concluded that rarefaction did not significantly increase resistance. However, a mathematical model study by Greene et al demonstrated that rarefaction of 42% of 3 rd or 4 th order vessels would lead to 21% increased resistance. This model was based on the hamster cheek pouch, which forms an idealized branching structure. This may have different characteristics to vascular beds that contribute more to peripheral resistance. Modeling techniques are not yet sufficiently advanced to describe interactions between hypertrophied vessels and rarefied networks. It has been suggested that vessel remodeling proximally and distal rarefaction will act in a synergistic manner  and the combination will lead to greater resistance than the simple product of each component. Sophisticated modeling may be the path for future research to establish the relative importance of observed changes in different vessels.
| Changes in the Renal Vessels|| |
The cardinal histological change seen in hypertensive kidneys is narrowing of the afferent arteriole. The classic studies by Sommers identified a spectrum of disorders throughout 1800 renal biopsies. This varied from focal spasm of arterioles with concentric overlapping of smooth muscle in the mildest cases to more severe changes with endothelial edema leading to luminal encroachment, smooth muscle hypertrophy, degenerative changes with hyalinization and irregular and focal luminal narrowing. Traditionally these changes were thought to develop after some years of established hypertension.  A recent study examined renal tissue from young adults who died traumatically and demonstrated a correlation between arteriolar narrowing with increasing incidence of hypertension in their country of origin.  These changes are not uniformly distributed through the kidney and will lead to relative ischemia in the more severely affected nephrons. Sealey  et al have proposed that the renin secreted by the ischemic nephrons will have a disproportionate effect on blood pressure. The majority of normal nephrons will ensure adequate renal function, and increases in blood pressure will tend to lead to correction through sodium natriuresis. However, this response will be incomplete due to the promotion of sodium retention though angiotensin II from the ischemic nephron population. This phenomenon may explain the variation between individuals responses to sodium loading, and the residual circulating renin in some hypertensive patients when renin should be suppressed by increased perfusion pressure.
The Origins of Vascular Structural Changes:
Developmental Relics or Compensatory Plasticity?
So far this review has described structural changes, which have been reported and commented on the hemodynamic alterations they produce. We have shown that vascular structure can influence renal function, peripheral vascular resistance and hence blood pressure. The second half of the review will outline a hypothetical basis for their occurrence. Recent epidemiological studies ,, have shown strong links between low birthweight and increased risk of hypertension. It has been proposed that events in early life permanently alter, or "program" subsequent development in favor of cardiovascular disease. These associations may be explained by distorted vascular development, consequent to the factors which impair intra-uterine growth.
Hypertrophy and rarefaction are maladaptive changes in view of the demonstrable decrease in mechanical efficiency that they cause and the vascular catastrophes that they predate, but they result from the same developmental principles that create efficient structures with minimal mechanical work. Control of vessel growth and development is determined by nutritive demands from the dependant tissues.  Feedback from the resulting flow in the form of shear stress and wall stress alters growth and development of cellular wall components. These processes determine embryonic development of a vascular tree and subsequent remodeling to the changing demands of the growing organism. This plasticity of vascular structure is retained in the mature adult and can be demonstrated in animal models.
The interaction between the ability of structures to remodel towards the ideal for their function, and the limits imposed by the other components of the cardiovascular system is shown in [Figure - 1], and can be illustrated by the following example.
Wall remodeling has been shown mathematically to reduce tension in the vessel wall when it is exposed to increased pressure  and is thus adaptive to the circumstances of that vessel. However remodeling results in luminal encroachment and increased resistance which increases the pressure loading on the system, and is maladaptive. This also illustrates the central idea of programming; where adaptive responses to circumstances early in life may become maladaptive for the adult organism.
We suggest that structural changes may be present at an early stage of development as a result of relative increases in flow and pressure in the growth-restricted fetus. These changes or an increased capacity to develop these changes may persist and manifest themselves in adult life as hypertension. To support our hypothesis, we will describe normal vascular development, animal experiments demonstrating retained adult plasticity and human studies showing altered vascular structure early in the development of hypertension.
| Vascular Embryology|| |
Vascular cells evolve from mesoderm, differentiating into blood cellular components and vessel components before flow is established. Growth of vessel walls is initially controlled by vascular endothelial growth factor that primarily leads to differentiation and division. As marshes of blood vessel components stir into flowing channels, tissue demands mediated through oxygen and adenosine as paracrine factors stimulate further growth.  A combination of vessel wall factors in response to circumferential and shear stress stimulates development of additional wall components and accumulates smooth muscle cells and extracellular matrix including elastic fibers that characterize arteries and arterioles. The cellular and molecular mechanisms governing this process are beginning to be identified and are comprehensively reviewed by Cowan and Langille.  Network factors are less well studied in vivo than cellular mechanisms. The methods by which genetic blueprints for a vascular tree or organogenesis are translated into functioning structures are beginning to be understood. A family of homebox genes have been identified and linked to tissue polarity in wing development in Drasophila  and myocardial repair in rats. 
| Plasticity of Mature Vasculature|| |
There are limits to the further differentiation of the mature vascular tree. Clearly it is not possible to grow a second aorta. Animal models suggest that there is considerable plasticity of vessels supplying muscles. Pig right ventricles hypertrophy in response to pulmonary artery banding. Hemodynamic studies of the right coronary arteries in these animals demonstrated no additional resistance compared to control arteries, which indicates that the increased demands of the muscle produce an ideal mechanically minimized network. The new network has an increased ratio of arterioles to capillaries. The number of vessel divisions from coronary ostium to capillary increased from 10 to 11. The increased branching begins in proximal vessels indicating residual plasticity in well differentiated structures. Tissue demands is not the sole stimulus to vessel growth in this model and it is possible that chronic vasodilatation and muscle tension is transformed into vascular growth.
Another model that demonstrates adult vascular plasticity is the cremaster muscle of rats with unilateral orchidectomy.  The operated side has diminished vessel density in an identical milieu other than loss of load bearing function of the muscle.
| Mathematical Modeling|| |
Mathematical models of vascular networks support the theory that shear stress and circumferential stress in combination as modifiers of growth can lead to idealised flow. Alternatively with different criteria in the model, the network would remodel into a single vessel. These models are relatively crude, limited to describing possible mechanisms to create capillary meshworks to supply homogenous tissue metabolic demands.
| Plasticity of Renal Vasculature|| |
Irregular involvement of nephrons in pathological responses could be accentuated in the presence of limited absolute nephron number. This theory was first outlined by Brenner in 1988.  Nephron number varies between individuals from 300,000 to 1,100,000,  and is determined at birth.  Further renal growth is finite and limited to increasing the size of components of the nephron. Individuals with numerically limited functional reserve are more susceptible to the pathological processes of high blood pressure described above. The supporting evidence is accumulating but is circumstantial. Populations with susceptibility to salt sensitive hypertension have been shown to have smaller average size of kidneys.  Experimental reduction of renal mass increases the risk of hypertension  as does surgical reduction in removal of renal tumors  or unilateral nephrectomy for donation.
| Programming of Vascular Structure|| |
Programming of hypertension has recently become a major research area investigating key epidemiological observations linking early development with cardiovascular mortality. Programming suggests that finite stages of development are windows of plasticity in which the limits of system responses are set. Sexual differentiation has been recognized for many years to depend upon a surge of male hormones to change the phenotype that would otherwise be female. However, within the last ten years numerous epidemiological studies have linked early life events to cardiovascular mortality ,, and have been performed in wealthy Western countries and in India., These studies traced adults from populations with detailed birth records and have shown correlations between low birth weight and later occurrence of hypertension. The variation in adult blood pressure is typically two mmHg per kg of birth weight
The epidemiologists who have produced this work believe maternal nutrition in pregnancy to be the cause of low birth weight and subsequent hypertension.
Our recent study of 635 young adults in Edinburgh demonstrated confounding influences in this relationship from maternal blood pressure, and birth weight, which might at least partially represent a marker for an inherited influence of hypertension.
| Vascular Structural Changes in Early Hypertension|| |
Evidence supporting programming of vascular structure as an important process in the development of hypertension comes from studies showing structural changes early in the process, especially in people with familial tendency to develop hypertension. Japanese subjects with a strong family history of hypertension have diminished reactive hyperemic forearm blood flow. Subjects with early essential hypertension characterized by higher cardiac output had capillary rarefaction demonstrated in conjunctival micrographs.
Familial determinants of blood pressure have been studied through a novel epidemiological method. The population attending a single medical center at Ladywell in Edinburgh had their blood pressure screened. By studying groups of offspring defined by a function of their own and their parents' blood pressure, factors associating with their familial tendency to develop high blood pressure can be separated from subsequent factors upon their blood pressure. Non-invasive studies of microvascular blood flow demonstrated abnormalities in the offspring who shared above average blood pressure with their parents.  They had 50% lower maximal blood flow in heated skin, [Figure - 2], and diminished capillary number following venous occlusion, [Figure - 3]. These abnormalities are of the same magnitude observed in established hypertension but the differences in blood pressure between the subject groups were small (6mmHg). Thus abnormalities in the microvasculature are present prior to a rise in pressure, and not present in everyone with a higher pressure, suggesting a possible causative role in the inherited rise in blood pressure.
These changes will tend to increase blood flow in the fewer vessels, which will provide, as we know from the animal studies, the stimulus to develop more vessels to correct the mismatch between growth and flow. Yet the abnormalities persist. This might be due to decreased sensitivity to the stimulus of increased flow or to the growth message transuded by that flow. Alternatively the peripheral microvesel structures may be an appropriate response to the pressure set by the kidney, which may have fewer nephrons or populations of ischemic nephrons influencing the pressure natriuresis relationship. All of these mechanisms could be programmed in utero and be worth investigating as possible explanations of the epidemiological observations
Whatever the precise mechanism, we can appreciate that these subtle maladaptations can develop, persist and feedback to increase peripheral resistance. Adaptive structural alterations from the ideal may be beneficial during times of rapid growth and development, or protective during nutritional insufficiency. However, they over burden the organism with the structural basis for ongoing maladaptations and the ultimate catastrophes of stroke or myocardial infarction.
| References|| |
|1.||Struijker Boudier HA, le Noble JL, Messing WW, Huijberts MS, le Noble FA, Van Essen H. The microcirculation and hypertension. J Hypertens Suppl 1992; 10:S147-56. |
|2.||Borders JL, Granger HJ. Power dissipation as a measure of peripheral resistance in vascular networks. Hypertension 1986;8: 184-91. [PUBMED] |
|3.||Prasad A, Dunnill GS, Mortimer PS, MacGregor GA. Capillary rarefaction in the forearm skin in essential hypertension. J Hypertens 1995;13:265-8. [PUBMED] |
|4.||Henrich HA, Romen W, Heimgartner W, Hartung E, Baumer F. Capillary rare faction characteristic of the skeletal muscle of hypertensive patients. Klin Wochenschr 1988;66:54-60. |
|5.||Pedrinelli R, Spessot M, Salvetti A. Reactive hyperemia during short-term blood flow and pressure changes in the hypertensive forearm. J Hypertens 1990; 8:467-71. [PUBMED] |
|6.||Harper RN, Moore MA, Marr MC, Watts LE, Hutchins PM. Arteriolar rarefaction in the conjunctiva of human essential hypertensives. Microvasc Res 1978; 16:369-72. [PUBMED] |
|7.||Chapman N, Mohamudally A, Cerutti A, et al. Retinal vascular network architecture in low-birth-weight men. J Hypertens 1997; 15:1449-53. [PUBMED] [FULLTEXT]|
|8.||Stanton AV, Wasan B, Cerutti A, et al. Vascular network changes in the retina with age and hypertension. J Hypertens Short DS. Arteries of the intestinal wall in systemic hypertension. Lancet 1995;13:1724-8. |
|9.||Short DS. Arteries of the international wallin systemic hypertension. Lancet 1958;ii:1261-3. |
|10.||Folkow B. Hypertensive structural changes in systemic precapillary resistance vessels: How important are they for in vivo hemo-dynamics? J Hypertens 1995;13:1546-59. [PUBMED] |
|11.||Guyton AC, Coleman TG, Cowley AV Jr, Scheel KW, Manning RD Jr, Norman RA Jr. Arterial pressure regulation. Overriding dominance of the kidneys in long-term regulation and in hypertension. Am J Med 1972;52:584-94. |
|12.||Bianchi G, Fox U, Di-Franccsco GF, Giovanetti AM, Pagetti D. Blood pressure changes produced by kidney cross-transplantation between spontaneously hypertensive rats and normotensive rats, din Sci Mol Med 1974;47:435-48. |
|13.||Dahl LK, Heine M. Primary role of renal homografts in setting chronic blood pressure levels in rats. Circ Res !975;36:692-6. |
|14.||Curtis JJ, Luke RG, Dustan HP. Remission of essential hypertension after renal transplantation. New EngI J Med 1983;309:1009-15. |
|15.||Schiffrin EL, Hayoz D. How to assess vascular remodeling in small and medium-sized muscular arteries in humans. J Hypertens 1997; 15:571-84. [PUBMED] [FULLTEXT]|
|16.||Baumbach GL, Heistad DD. Remodeling of cerebral arterioles in chronic hyper tension. Hypertension 1989;13:968-72. [PUBMED] |
|17.||Heagerty AM, Aalkjaer C, Bund SJ, Korsgaard N, Mulvany MJ. Small artery structure in hypertension. Dual processes of remodeling and growth. Hypertension 1993;21:391-7. |
|18.||Short D. Morphology of the intestinal arterioles in chronic human hypertension. Br Heart J I966;28:184-92. |
|19.||Gasser P, Buhler FR. Nailfold microcirculation in normotensive and essential hypertensive subjects, as assessed by video microscopy. j Hypertens 1992;10:83-6. |
|20.||Hashimoto H, Prewitt RL, Efaw CW. Alterations in the microvasculature of one-kidney, one-clip hypertensive rats. Am J Physiol 1987;253:H933-40. [PUBMED] [FULLTEXT]|
|21.||Boegehold MA, Johnson MD, Overbeck HW. Pressure-independent arteriolar rarification in hypertension. Am J Physiol 1991;261:H83-7. [PUBMED] [FULLTEXT]|
|22.||Gobe G, Browning J, Howard T, Hogg N, Winterford C, Cross R. Apoptosis occurs in endothelial cells during hypertension-induced microvascular rarefaction. J Struct Biol 1997; 118:63-72. |
|23.||Pickering GW. The vascular physiology in hypertension. Adv Intern Med 1950;4:445-2. [PUBMED] |
|24.||Folkow B, Grimby G, Thulesius O. Adaptive structural changes in the vascular walls in hypertension and their relation to the control of peripheral resistance. Acta Physiol Scand 1957;44: 255-72. |
|25.||Hallback M, Gothberg G, Lundin S, Ricksten SE, Folkow B. Hemodynamic consequences of resistance vessel rarification and of changes in smooth muscle sensitivity. Acta Physiol Scand 1976;97:233-40. |
|26.||Greene AS, Toneliato PJ, Lui J, Lombard JH, Cowley AW Jr. Microvascular rare faction and tissue vascular resistance in hypertension. Am J Physiol 1989; 256: H126-31. |
|27.||Zweifach BW. The microcirculation in experimental hypertension. State-of-theart review. Hypertension 1983;5:I10-6. |
|28.||Castleman B, Smithwick RH. The relation of vascular disease to the hypertensive state: II. The adequacy of the renal biopsy as determined from a study of 500 patients. New Engl J Med 1948;239:729-36. |
|29.||Tracy RE, Malcom GT, Oalmann MC, Qureshi U, Ishii T, Velez-Duran M. Renal microvascular features of hypertension in Japan, Guatemala, and the United States. Arch Pathol Lab Med I992;l 16:50-5. |
|30.||Sealey JE, Biumenfeld JD, Bell GM, Pecker Ms, Somemers SC, Laragh JH. On the renal basis for essential hypertension: nephron heterogeneity with discordant rennin secretion and sodium excretion causing a hypertensive vasoconstriction-volume relationship. J Hypertens 1988;6:763-77. |
|31.||Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 1989;298:564-7. [PUBMED] [FULLTEXT]|
|32.||Barker DJ, Bull AR, Osmond C, Simmonds SJ. Fetal and placental size and risk of hypertension in adult life. BMJ 1990;301: 259-62. [PUBMED] [FULLTEXT]|
|33.||Barker DJ, Godfrey KM, Osmond C, Bull A. The relation of fetal length, ponderal index and head circumference to blood pressure and the risk of hypertension in adult life. Paediatr Perinat Epidemiol 1992;6:35-44. [PUBMED] |
|34.||Adair TH, Gay WJ, Montani JP. Growth regulation of the vascular system: evidence for a metabolic hypothesis. Am J Physiol 1990;259:R393-404. [PUBMED] [FULLTEXT]|
|35.||Risau W. Mechanisms of angiogenesis. Nature 1997;386:671-4. [PUBMED] [FULLTEXT]|
|36.||Cowan DB, Langille BL. Cellular and molecular biology of vascular remodeling. CurrOpinLipidol 1996;7:94-100. |
|37.||Blankesteijn WM, Essers-Janssen YP, Ulrich MM, Smits JF, Increased expression of a homologue of Drosophila tissue polarity gene 'frizzled' in left ventricular hypertrophy in the rat, as identified by subtractivc hybridization. J Mol CellCardiol 1996:28:1187-91. |
|38.||De Robertis EM, Oliver G, Wright CV. Homeobox genes and the vertebrate body plan. Sci Am 1990;263:46-52. |
|39.||White FC, Nakatani Y, Nimmo L, Bloor CM. Compensatory angiogenesis during progressive right ventricular hypertrophy. Am J Cardiovasc Pathol 1992;4:51-68. [PUBMED] |
|40.||Wang DH, Prewitt RL. Microvascular development during normal growth and reduced blood flow: Introduction of a new model. Am J Physiol 1991;260:H 1966-72. |
|41.||Kiani MF, Hudetz AG. Computer simulation of growth of anastomosing micro-vascular networks. J Theor Biol 1991;150:547-60. [PUBMED] |
|42.||Hacking WJ, VanBavel E, Spaan JE. Shear stress is not sufficient to control growth of vascular networks: a model study. Am J Physiol I996;270:H364-75. |
|43.||Mackenzie HS, Brenner BM. Fewer nephrons at birth: a missing link in the etiology of essential hypertension? Am J Kidney Dis 1995;26:91-8. [PUBMED] |
|44.||Nyengaard JR, Bendtsen TF. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec 1992;232:194-201. [PUBMED] |
|45.||Luft FC, Rankin LI, Bloch R, et al. Cardiovascular and humoral responses to extremes of sodium intake in normal black and white men. Circulation 1979;60:697-706. [PUBMED] |
|46.||Brenner BM. Nephron adaptation to renal injury or ablation. Am J Physiol 1985;249: F324-37. [PUBMED] [FULLTEXT]|
|47.||Novick AC, Gephardt G, GuzB, Steinmuller D, Tubbs RR. Long-term follow-up after partial removal of a solitary kidney. New Engl J Med 1991;325:1058-62. |
|48.||Haberal M, Karakayali H, Moray G, Demirag A, Yildirim S, Bilgin N. Longterm follow-up of 102 living kidney donors. Clin Nephrol 1998;50:232-5. [PUBMED] |
|49.||Fall CH, Stein CE, Kumaran K, et al. Size at birth, maternal weight, and type 2 diabetes in South India. Diabet Med 1998;15:220-7. [PUBMED] |
|50.||Stein CE, Fall CH, Kumaran K, Osmond C, Cox V, Barker DJ. Fetal growth and coronary heart disease in south India. Lancet 1996;348:1269-73. [PUBMED] [FULLTEXT]|
|51.||Law CM, Shiell AW. Is blood pressure inversely related to birth weight? The strength of evidence from a systematic review of the literature. J Hypertens 1996; 14:935-41. |
|52.||Walker BR, McConnachie A, Noon JP, Webb DJ, Watt GC. Contribution of parental blood pressures to association between low birthweight and adult high blood pressure: cross-sectional study. BMJ 1998;316:834-7. [PUBMED] [FULLTEXT]|
|53.||Takeshita A, Imaizumi T, Ashihara T, et al. Limited maximal vasodilator capacity of forearm resistance vessels in normotensive young men with a familial predisposition to hypertension. Circ Res 1982; 50:671-7. [PUBMED] |
|54.||Sullivan JM, Prewitt RL, Josephs JA. Attenuation of the microcirculation in young patients with high-output borderline hypertension. Hypertension 1983;5:844-51. [PUBMED] |
|55.||Noon JP, Walker BR, Webb DJ, et al. Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure. J Clin Invest 1997;99:1873-9. [PUBMED] [FULLTEXT]|
R John Irving
Department of Medical Sciences, University of Edinburgh, Western General Hospital, Crewe Road South Edinburgh, Scotland, EH4 2XU
[Figure - 1], [Figure - 2], [Figure - 3]
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