α‐Adrenergic Control of Skeletal Muscle Circulation at Rest and During Exercise in Aging Humans

Dinenno, Frank A.; Joyner, Michael J.

doi:10.1080/10739680600618843

Cited by 65 publications

(70 citation statements)

References 82 publications

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“…In addition, several recent studies have identified clear limb-specific responses to pharmacological and physiological stimuli, 22 as well as significant differences in tonic vasoconstriction between limbs in the elderly. 23 Thus, the current data extend this earlier work in the forearm, demonstrating for the first time a significant increase in AT 1 receptor sensitivity in the leg vasculature of healthy elderly individuals at rest. Although the mechanism for increased AT 1 responsiveness may be as simple as receptor upregulation in response to reduced substrate, 24 this pathway may become an increasingly important regulator of peripheral hemodynamics with advancing age.…”

Section: At 1 Receptor Sensitivity At Restsupporting

confidence: 78%

Angiotensin II in the Elderly

et al. 2008

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Abstract-Exercise hyperemia is attenuated in the elderly, which may be attributed to local vasoregulatory pathways within the skeletal muscle vasculature. Therefore, we sought to determine whether healthy aging is associated with changes in angiotensin II (Ang II) receptor sensitivity through measurements of leg blood flow in resting and exercising skeletal muscle. In 12 (nϭ6 young, 24Ϯ1 years; nϭ6 older, 68Ϯ3 years) healthy volunteers, we determined changes in leg blood flow (ultrasound Doppler) before and during intra-arterial infusion of Ang II (0.8 ng/mL of leg blood flow per minute). Heart rate, arterial blood pressure, common femoral artery diameter, and mean blood velocity were measured at rest and during knee-extensor exercise at 20% and 40% of the maximal work rate (WR max ). At rest, Ang II infusion decreased leg blood flow to a greater extent in older (Ϫ61Ϯ8%) subjects compared with younger subjects (Ϫ31Ϯ5%). Compared with rest, Ang II-mediated vasoconstriction (leg blood flow) during exercise was diminished in both older and younger subjects at 20% (older: Ϫ7Ϯ5%; younger: Ϫ21Ϯ2%) and 40% WR max (older: Ϫ5Ϯ4%; younger: Ϫ9Ϯ3%). These data identify a clear age-related hypersensitivity to Ang II in the resting leg, which may contribute to the recognized decrement in leg blood flow in this cohort. However, the diminished vasoconstriction to Ang II during exercise suggests that the elevation in Ang II type 1 receptor sensitivity documented at rest does not contribute significantly to the blunted exercise hyperemia experienced with advancing age. Key Words: basic science Ⅲ elderly Ⅲ blood flow regulation Ⅲ exercise Ⅲ angiotensin receptors A ngiotensin II (Ang II) acts as a potent endogenous vasoconstrictor through binding to the Ang II type 1 (AT 1 ) receptor on arteriolar vascular smooth muscle. With advancing age, there is a notable decline in plasma renin activity 1 accompanied by small decrements in circulating Ang II 2 and an increase in AT 1 receptor density. 3,4 However, the functional consequence of this age-related adaptation of the renin-angiotensin system on the peripheral circulation is not well understood. Although the pressor response to systemic Ang II infusion is elevated with age, 5 no age-specific adaptation in AT 1 receptor sensitivity has been observed with local, intra-arterial Ang II infusion in the arm. 6 Together, these studies indicate a general decline in renin-angiotensin system function with age but with uncertainty as to the impact of these changes on end-organ function and skeletal muscle hemodynamics.AT 1 receptor sensitivity to Ang II in the elderly may be especially important in the context of underlying changes in autonomic function. It is well established that elevated vasoconstrictor tone as a consequence of high sympathetic nerve activity is present in healthy, older adults, 7-9 despite a reduction in the sensitivity of postjunctional adrenergic vascular receptors. 10 This capacity for sustained sympathetic vasoconstriction in the face of reduced adrenergic responsivenes...

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Section: At 1 Receptor Sensitivity At Restsupporting

confidence: 78%

Angiotensin II in the Elderly

et al. 2008

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“…However, the larger fall in BP in older men when no bursts of MSNA were present suggests a greater sympathetic vasoconstrictor tone under resting conditions that appears selective to this group. Given the known attenuation of ␣-adrenergic receptor responsiveness in older men (5,6), these data suggest higher resting MSNA burst frequency is somewhat compensating and providing a greater sympathetic constrictor support of BP. Interestingly, this effect is not present in older women.…”

Section: Discussionmentioning

confidence: 86%

Influence of age and sex on the pressor response following a spontaneous burst of muscle sympathetic nerve activity

Vianna

Hart

Fairfax

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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The sympathetic nervous system is critical for the beat-to-beat regulation of arterial blood pressure (BP). Although studies have examined age- and sex-related effects on BP control, findings are inconsistent and limited data are available in postmenopausal women. In addition, the majority of studies have focused on time-averaged responses without consideration for potential beat-to-beat alterations. Thus we examined whether the ability of muscle sympathetic nerve activity (MSNA) to modulate BP on a beat-to-beat basis is affected by age or sex. BP and MSNA were measured during supine rest in 40 young (20 men) and 40 older (20 men) healthy subjects. Beat-to-beat fluctuations in mean arterial pressure (MAP) were characterized for 15 cardiac cycles after each MSNA burst using signal averaging. The rise in MAP following an MSNA burst was similar between young men and women (+2.64 ± 0.3 vs. +2.57 ± 0.3 mmHg, respectively). However, the magnitude of the increase in MAP after an MSNA burst was reduced in older compared with young subjects (P < 0.05). Moreover, the attenuation of the pressor response was greater in older women (+1.20 ± 0.1 mmHg) compared with older men (+1.72 ± 0.2 mmHg; P < 0.05). Interestingly, in all groups, MAP consistently decreased after cardiac cycles without MSNA bursts (nonbursts) with the magnitude of fall greatest in older men. In summary, healthy aging is associated with an attenuated beat-to-beat increase in BP after a spontaneous MSNA burst, and this attenuation is more pronounced in postmenopausal women. Furthermore, our nonburst findings highlight the importance of sympathetic vasoconstrictor activity to maintain beat-to-beat BP, particularly in older men.

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“…In this regard, in the present study, DBP, which primarily reflects vasomotor tone, was unchanged during exercise in older subjects, whereas it was significantly reduced from rest in young subjects. Although age-related impairments in vasodilatation or metabolic modulation of sympathetic outflow directed to the skeletal muscle vasculature may be implicated (9,15), it is also possible that diminished baroreflex control of the vasculature during exercise in older subjects may make an important contribution to the augmented increase in blood pressure.…”

Section: Discussionmentioning

confidence: 99%

Influence of age on cardiac baroreflex function during dynamic exercise in humans

Fisher¹,

Ogoh²,

Ahmed³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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We investigated the influence of aging on cardiac baroreflex function during dynamic exercise in seven young (22 Ϯ 1 yr) and eight older middle-aged (59 Ϯ 2 yr) healthy subjects. Carotid-cardiac baroreflex function was assessed at rest and during moderate-intensity steadystate cycling performed at 50% heart rate reserve (HRR). Five-second pulses of neck pressure and neck suction from ϩ40 to Ϫ80 Torr were applied to determine the operating point gain (GOP) and maximal gain (GMAX) of the full carotid-cardiac baroreflex function curve and examine baroreflex resetting during exercise. At rest, mean arterial pressure (MAP) and heart rate were similar between the younger and older subjects. In contrast, the resting GOP and GMAX were significantly lower in the older subjects. The increase in MAP from rest to exercise was greater in the older subjects (⌬ ϩ20 Ϯ 2 older vs. ⌬ ϩ6 Ϯ 3 younger mmHg; P Ͻ 0.001). However, the GOP was similar in both groups during exercise because of a reduction in the younger subjects. In contrast, GMAX was unchanged from rest and therefore remained lower in older subjects (Ϫ0.19 Ϯ 0.05 older vs. Ϫ0.42 Ϯ 0.05 younger beats ⅐ min Ϫ1 ⅐ mmHg Ϫ1 ; 50% HRR; P Ͻ 0.001). Furthermore, exercise resulted in an upward and rightward resetting of the cardiac baroreflex function curve in both groups. Collectively, these findings suggest that the cardiac baroreflex function curve appropriately resets during exercise in older subjects but operates at a reduced GMAX primarily because of age-related reductions in carotidcardiac control manifest at rest. arterial baroreceptors; aging; heart rate HEALTHY AGING HAS BEEN associated with impaired arterial baroreflex control of heart rate (HR; see Refs. 10,17,25,33), vasomotor tone (8), and blood pressure (23) under resting conditions. However, little is known about how aging alters baroreflex function during dynamic exercise. Importantly, alterations noted at rest cannot simply be extrapolated to exercise because peripheral feedback from skeletal muscle (i.e., exercise pressor reflex; EPR) and feedforward central neural inputs (i.e., central command) modulate arterial baroreflex control during exercise, influencing reflex sensitivity and also contributing to the resetting of the baroreflex function curve (13,27). Moreover, EPR function may be attenuated in older subjects (24), thereby leading to decreases in input from the EPR to the baroreflex, potentially altering baroreflex sensitivity and resetting characteristics. In addition, it is possible that an agerelated enhancement of central command may also modify the baroreflex during exercise (5). Thus it is important to consider the influence of healthy aging on baroreflex function and resetting during dynamic exercise. This is particularly relevant from a clinical standpoint since older subjects are increasingly being encouraged to exercise and decreases in baroreflex control of HR can increase the occurrence of ventricular arrhythmias during physical activity (1,38).Limited studies have attempted to investigate ag...

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α‐Adrenergic Control of Skeletal Muscle Circulation at Rest and During Exercise in Aging Humans

Cited by 65 publications

References 82 publications

Angiotensin II in the Elderly

Angiotensin II in the Elderly

Influence of age and sex on the pressor response following a spontaneous burst of muscle sympathetic nerve activity

Influence of age on cardiac baroreflex function during dynamic exercise in humans

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