Effects of Aging and Hypertension on the Microcirculation

Abstract

Abstract-Alterations of structure and function of the microcirculation in hypertension in the elderly and changes with normotensive aging have not been fully clarified. We studied capillary pressure, density, and skin microvascular function in 46 subjects in 3 groups: elderly subjects (aged Ͼ60 years) with untreated hypertension (nϭ16), elderly normotensive subjects (nϭ16), and young normotensive subjects (age Ͻ45 years, nϭ14). In a subgroup of 19 subjects, we also studied resistance artery function in the isometric myograph. Capillary pressure was higher in both elderly groups (elderly hypertensives: 18.6Ϯ4.7 mm Hg, elderly normotensives: 17.6Ϯ4.0 mm Hg) compared with young normotensives (13.9Ϯ2.6 mm Hg, PϽ0.05), but capillary density did not differ between the groups. Skin vasodilating responses to acetylcholine were greater in young normotensives compared with both elderly groups (PϽ0.05). In isolated resistance arteries, there was a greater inhibitory effect from blockade of the L-arginine-NO pathway in elderly normotensives (PϽ0.05) and a reduction in the maximal inhibitory effect of combined blockade of NO, prostanoids, and endothelium-derived hyperpolarizing factor in elderly hypertensives (PϽ0.05). This study has demonstrated a significant effect of aging but no additional effect of hypertension on capillary pressure and no effect of either on capillary density. Our findings with both in vivo and in vitro methods suggest that normotensive aging may depend on relative preservation of NO-dependent vasodilatation in resistance arteries at the expense of a rise in capillary pressure. Key Words: microcirculation Ⅲ capillaries Ⅲ endothelium Ⅲ endothelium-derived relaxing factors Ⅲ aging A lterations of structure and function in the microcirculation are important factors in vascular disease states, such as hypertension and diabetes mellitus. 1 Capillary pressure is increased in essential hypertension, 2 and this may be because of decreased capillary numbers 3-5 or abnormalities in vascular responses at a precapillary or postcapillary level. 6,7 Both capillary rarefaction and abnormal microvascular responses have been observed before the development of clinical hypertension, 8,9 implicating these processes in pathogenesis.Aging is associated with endothelial dysfunction, possibly because of a decline in NO and prostanoid pathways, 10 -12 yet hypertension in the elderly is predominantly a systolic abnormality, 13 considered to be mainly because of altered large artery stiffness. 14 Whether microvascular structure and function is also abnormal in hypertension in the elderly has not been fully clarified. We, therefore, conducted the present study to examine whether aging, in the absence of changes in blood pressure (BP), is associated with abnormalities in the structure and function of the microcirculation, and whether, in older subjects, hypertension exacerbates any of the abnormalities observed. Methods Study SubjectsThe study was approved by the local research ethics committee and conducted according to the prin...

Hypertension

“…49 At variance with these reports, rarefaction was not found in dorsal finger skin of elderly subjects with mainly systolic hypertension. 11 There is some evidence that capillary rarefaction in the skin may antedate the clinical onset of essential hypertension. In 2 other studies by Antonios et al, 50 dorsal finger venous occlusion capillaroscopy revealed an abnormally low capillary density in borderline hypertensive subjects and even in normotensive subjects with a familial predisposition to the disease.…”

“…Except in specialized microvascular beds, such as the renal glomerulus, normal systemic capillary pressure (here, we disregard the pulmonary circulation, which is not relevant to the field of systemic hypertension) is relatively low (10 to 30 mm Hg). 11 Elevation of systemic capillary pressure above this range has several potentially deleterious effects, including the following: (1) interstial edema, which can have dramatic effects on the brain as exemplified in hypertensive encephalopathy 12 ; (2) disruption of capillary wall structure, with extravasation of plasma proteins and blood cells 13 ; and (3) activation of the microvascular endothelium, which may trigger or amplify an inflammatory cascade, 14 of importance, for example, in the pathogenesis of venous ulcers. 15 Pleiotropic changes in the functional behavior of arterioles have been noted in both clinical and experimental hypertension, including hyperresponsiveness to vasoconstrictor stimuli, 16,17 leading to their constriction or even complete closure, 16,18,19 endothelial dysfunction, 20,21 and reduced bioactivity of endothelium-derived NO.…”

Comparison of the retinal microvasculature in European and African-Caribbean people with diabetes

“…In hypertension elevated BP results in widespread 'remodelling' of small arteries and arterioles [6], a process that probably involves both functional and structural changes [7]. Remodelling contributes to the elevated peripheral vascular resistance that is a feature of established hypertension [8], but may also protect the microvasculature downstream from the elevated systemic blood pressure [9]. In the eye microvascular 'remodelling' is manifest as a narrowing of retinal arteriolar diameters [10][11][12] and reduced arteriolar density or number [11;13].…”

Phenotyping the Microcirculation

“…17 He et al 18 showed recently that modest salt reduction can restore capillary density in patients with mild hypertension. Shore and coworkers 19,20 have, in addition to capillary density, measured capillary pressures in the skin of hypertensive individuals. Capillary pressure was higher in both elderly normotensives and hypertensives than in young normotensives, suggesting a significant effect of aging rather than hypertension, per se, on capillary pressure.…”