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      Cardiovascular and hormonal responses to static handgrip in young and older healthy men

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          Abstract

          The purpose of this study was to investigate the effect of age on cardiovascular changes and plasma concentrations of adrenomedullin (ADM), catecholamines, endothelin-1 (ET-1) and plasma renin activity (PRA) in healthy men. A total of 15 young (21 ± 0.3 years) and 15 older (64 ± 0.7 years) healthy men performed two 3-min bouts of static handgrip at 30% of maximal voluntary contraction, alternately with each hand without any break between the bouts. During exercise heart rate (HR), blood pressure (BP), stroke volume (SV) and pre-ejection period (PEP) and left ventricle ejection time (LVET) were measured. Blood samples were taken before exercise, at the end of both exercise bouts and in the fifth minute of the recovery period. The handgrip-induced increases in HR and cardiac output were significantly smaller in older than in young men ( p < 0.01). SV decreased only in older men ( p < 0.001). There were no differences between groups in BP increases. The baseline plasma ADM and catecholamines were higher in older man compared to young subjects. Handgrip caused increases in plasma ADM, ET-1 and PRA only in older men ( p < 0.05). The increases in plasma ADM correlated positively with those of noradrenaline (NA), PRA, ET-1 and LVET and negatively with changes in total peripheral resistance (TPR), SV, PEP and PEP/LVET ratio. The increases in plasma ET-1 correlated positively with those of NA, PRA, TPR, mean BP and SV. These results revealed that ADM, ET-1 and angiotensin II can contribute to maintain vascular tone during static exercise in older but not in younger men.

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          Invited review: aging and the cardiovascular system.

          Aging is associated with complex and diversified changes of cardiovascular structure and function. The heart becomes slightly hypertrophic and hyporesponsive to sympathetic (but not parasympathetic) stimuli, so that the exercise-induced increases in heart rate and myocardial contractility are blunted in older hearts. The aorta and major elastic arteries become elongated and stiffer, with increased pulse wave velocity, evidence of endothelial dysfunction, and biochemical patterns resembling early atherosclerosis. The arterial baroreflex is sizably altered in aging, but different components are differentially affected: there is a definite impairment of arterial baroreceptor control of the heart but much better preserved baroreceptor control of peripheral vascular resistance. Alterations at the afferent, central neural, efferent, and effector organ portions of the reflex arch have been claimed to account for age-related baroreflex changes, but no conclusive evidence is available on this mechanistic aspect. Reflexes arising from cardiopulmonary vagal afferents are also blunted in aged individuals. The cardiovascular and reflex changes brought about by aging may have significant implications for circulatory homeostasis in health and disease.
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            Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase.

            To determine whether impaired endothelium-dependent dilation (EDD) in older adults is associated with changes in the expression of major vasoconstrictor or vasodilator proteins in the vascular endothelium, endothelial cells (EC) were obtained from the brachial artery and peripheral veins of 56 healthy men, aged 18-78 yr. Brachial artery EC endothelin-1 (ET-1) [0.99 +/- 0.10 vs. 0.57 +/- 0.10 ET-1/human umbilical vein EC (HUVEC) intensity, P = 0.01] and serine 1177 phosphorylated endothelial nitric oxide synthase (PeNOS) (0.77 +/- 0.09 vs. 0.44 +/- 0.07 PeNOS/HUVEC intensity, P < 0.05) (quantitative immunofluorescence) were greater, and EDD (peak forearm blood flow to intrabrachial acetylcholine) was lower (10.2 +/- 0.9 vs. 14.7 +/- 1.7 ml.100 ml(-1).min(-1), P < 0.05) in older (n = 18, 62 +/- 1 yr) vs. young (n = 15, 21 +/- 1 yr) healthy men. EDD was inversely related to expression of ET-1 (r = -0.39, P < 0.05). Brachial artery EC eNOS expression did not differ significantly with age, but tended to be greater in the older men (young: 0.23 +/- 0.03 vs. older: 0.33 +/- 0.07 eNOS/HUVEC intensity, P = 0.08). In the sample with venous EC collections, EDD (brachial artery flow-mediated dilation) was lower (3.50 +/- 0.44 vs. 7.68 +/- 0.43%, P < 0.001), EC ET-1 and PeNOS were greater (P < 0.05), and EC eNOS was not different in older (n = 23, 62 +/- 1 yr) vs. young (n = 27, 22 +/- 1 yr) men. EDD was inversely related to venous EC ET-1 (r = -0.37, P < 0.05). ET-1 receptor A inhibition with BQ-123 restored 60% of the age-related impairment in carotid artery dilation to acetylcholine in B6D2F1 mice (5-7 mo, n = 8; 30 mo, n = 11; P < 0.05). ET-1 expression is increased in vascular EC of healthy older men and is related to reduced EDD, whereas ET-1 receptor A signaling tonically suppresses EDD in old mice. Neither eNOS nor PeNOS is reduced with aging. Changes in ET-1 expression and bioactivity, but not eNOS, contribute to vascular endothelial dysfunction with aging.
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              Age-associated cardiovascular changes in health: impact on cardiovascular disease in older persons.

              In the United States, cardiovascular disease, e.g., atherosclerosis and hypertension, that lead to heart failure and stroke, is the leading cause of mortality, accounting for over 40 percent of deaths in those aged 65 years and above. Over 80 percent of all cardio-vascular deaths occur in the same age group. Thus, age, per se, is the major risk factor for cardiovascular disease. Clinical manifestations and prognosis of these cardiovascular diseases likely become altered in older persons with advanced age because interactions occur between age-associated cardiovascular changes in health and specific pathophysiologic mechanisms that underlie a disease. A fundamental understanding of age-associated changes in cardiovascular structure and function ranging in scope from humans to molecules is required for effective and efficient prevention and treatment of cardiovascular disease in older persons. A sustained effort over the past two decades has been applied to characterize the multiple effects of aging in health on cardiovascular structure and function in a single study population, the Baltimore Longitudinal Study on Aging. In these studies, community dwelling, volunteer participants are rigorously screened to detect both clinical and occult cardiovascular disease and characterized with respect to lifestyle, e.g. exercise habits, in an attempt to deconvolute interactions among lifestyle, cardiovascular disease and the aging process in health. This review highlights some specific changes in resting cardiovascular structure and function and cardiovascular reserve capacity that occur with advancing age in healthy humans. Observations from relevant experiments in animal models have been integrated with those in humans to provide possible mechanistic insight.
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                Author and article information

                Contributors
                +48-22-6086518 , krzem@cmdik.pan.pl
                Journal
                Eur J Appl Physiol
                European Journal of Applied Physiology
                Springer-Verlag (Berlin/Heidelberg )
                1439-6319
                1439-6327
                28 July 2011
                28 July 2011
                April 2012
                : 112
                : 4
                : 1315-1325
                Affiliations
                Department of Applied Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego str, 02-106 Warsaw, Poland
                Author notes

                Communicated by Niels H. Secher.

                Article
                2069
                10.1007/s00421-011-2069-y
                3299973
                21796411
                6516800c-0fdc-49a3-aaf3-465cd6bf6f9a
                © The Author(s) 2011
                History
                : 29 September 2010
                : 29 June 2011
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag 2012

                Anatomy & Physiology
                systolic time intervals,aging,catecholamines,endothelin 1,adrenomedullin,exercise,hemodynamics,plasma renin activity

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