Enhanced metaboreflex sensitivity in hypertensive humans

Sausen, Mark; Delaney, Erin P.; Stillabower, Michael; Farquhar, William B.

doi:10.1007/s00421-008-0910-8

Cited by 63 publications

(74 citation statements)

References 29 publications

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“…There is emerging evidence that hypertension is associated with excessive pressor responses during muscle contraction; both mechanically (mechanoreflex) and metabolically (metaboreflex) driven components of the pressor reflex are suggested being involved [21,22]. Patients with hypertension were shown to produce exaggerated BP elevation and enhanced muscle sympathetic nerve activation during isometric handgrip exercise compared with age-related healthy controls [23,24]. Increased muscle metaboreflex activation leading to augmented pressor responses was demonstrated in older moderately hypertensive adults [25] and in pre-hypertensive state [26].…”

Section: Discussionmentioning

confidence: 99%

Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus?

Körei

Kempler

Istenes

et al. 2016

CVP

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Section: Discussionmentioning

confidence: 99%

Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus?

Körei

Kempler

Istenes

et al. 2016

CVP

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“…Adults with hypertension have abnormal pressor responses to exercise (11,28,58) that are mediated, in part, by EPR dysfunction (11,52). In the current study, we confirm and extend these previous findings and demonstrate that impaired EPR function contributes to exaggerated neurocirculatory responses to muscle contraction in a group of older adults with moderately elevated resting systolic BP in the combined highnormal and stage I hypertensive ranges.…”

Section: Discussionmentioning

confidence: 99%

Exaggerated exercise pressor reflex in adults with moderately elevated systolic blood pressure: role of purinergic receptors

Greaney

Matthews

Boggs

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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The neurocirculatory responses to exercise are exaggerated in hypertension, increasing cardiovascular risk, yet the mechanisms remain incompletely understood. The aim of this study was to examine the in vitro effectiveness of pyridoxal-5-phosphate as a purinergic (P2) receptor antagonist in isolated murine dorsal root ganglia (DRG) neurons and the in vivo contribution of P2 receptors to the neurocirculatory responses to exercise in older adults with moderately elevated systolic blood pressure (BP). In vitro, pyridoxal-5-phosphate attenuated the ATP-induced increases in [Ca 2ϩ ]i (73 Ϯ 15 vs. 11 Ϯ 3 nM; P Ͻ 0.05). In vivo, muscle sympathetic nerve activity (MSNA; peroneal microneurography) and arterial BP (Finometer) were assessed during exercise pressor reflex activation (static handgrip followed by postexercise ischemia; PEI) during a control trial (normal saline) and localized P2 receptor blockade (pyridoxal-5-phosphate). Compared with normotensive adults (63 Ϯ 2 yr, 117 Ϯ 2/70 Ϯ 2 mmHg), adults with moderately elevated systolic BP (65 Ϯ 1 yr, 138 Ϯ 5/79 Ϯ 3 mmHg) demonstrated greater increases in MSNA and BP during handgrip and PEI. Compared with the control trial, local antagonism of P2 receptors during PEI partially attenuated MSNA (39 Ϯ 4 vs. 34 Ϯ 5 bursts/min; P Ͻ 0.05) in adults with moderately elevated systolic BP. In conclusion, these data demonstrate pyridoxal-5-phosphate is an effective P2 receptor antagonist in isolated DRG neurons, which are of particular relevance to the exercise pressor reflex. Furthermore, these findings indicate that exercise pressor reflex function is exaggerated in older adults with moderately elevated systolic BP and further suggest a modest role of purinergic receptors in evoking the abnormally large reflex-mediated increases in sympathetic activity during exercise in this clinical population.hypertension; metaboreflex; muscle sympathetic nerve activity; calcium imaging; dorsal root ganglia AUGMENTED PRESSOR RESPONSES to exercise are associated with adverse cardiovascular and cerebrovascular events during and after physical activity (22,34,45). Additionally, nonhypertensive individuals with an exaggerated blood pressure (BP) response to exercise are more likely to develop clinical hypertension (12, 53) and are at higher risk of cardiovascular death compared with those with a normal BP response (57, 61). This risk is further modified by baseline hypertension status (61), making exaggerated BP responses to acute exercise especially problematic in adults with chronically elevated resting BP. Resting systolic BP increases with advancing age, such that ϳ65% of older adults have a resting systolic BP in the high-normal or stage I hypertensive range (i.e., 130 -159 mmHg) (5, 16, 40). Therefore, examining neurocirculatory regulation during exercise in this population is clinically relevant.Muscle contraction causes intensity-dependent increases in arterial BP, heart rate (HR), and sympathetic nerve activity (SNA). Afferent feedback from the exercising skeletal muscle is an import...

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“…During static handgrip exercise, central command increases heart rate and cardiac output by withdrawing parasympathetic tone (15), whereas the metabolic component of the EPR (i.e., muscle metaboreflex) is primarily responsible for the intensity-dependent increase in MSNA and peripheral vasoconstriction (30,45). A number of studies have examined the muscle metaboreflex in subjects with risk factors for T2D (e.g., obesity) and have yielded mixed results (9,29,35,40,41,52). Surprisingly, there is a paucity of studies examining the muscle metaboreflex in subjects with overt T2D.…”

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confidence: 99%

Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients

Holwerda

Restaino

Manrique

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Holwerda SW, Restaino RM, Manrique C, Lastra G, Fisher JP, Fadel PJ. Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients. Am J Physiol Heart Circ Physiol 310: H300 -H309, 2016. First published November 13, 2015; doi:10.1152/ajpheart.00636.2015.-Previous studies have reported exaggerated increases in arterial blood pressure during exercise in type 2 diabetes (T2D) patients. However, little is known regarding the underlying neural mechanism(s) involved. We hypothesized that T2D patients would exhibit an augmented muscle metaboreflex activation and this contributes to greater pressor and sympathetic responses during exercise. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured in 16 patients with T2D (8 normotensive and 8 hypertensive) and 10 healthy controls. Graded isolation of the muscle metaboreflex was achieved by postexercise ischemia (PEI) following static handgrip performed at 30% and 40% maximal voluntary contraction (MVC). A cold pressor test (CPT) was also performed as a generalized sympathoexcitatory stimulus. Increases in MAP and MSNA during 30 and 40% MVC handgrip were augmented in T2D patients compared with controls (P Ͻ 0.05), and these differences were maintained during PEI (MAP: 30% MVC PEI: T2D, ⌬16 Ϯ 2 mmHg vs. controls, ⌬8 Ϯ 1 mmHg; 40% MVC PEI: T2D, ⌬26 Ϯ 3 mmHg vs. controls, ⌬16 Ϯ 2 mmHg, both P Ͻ 0.05). MAP and MSNA responses to handgrip and PEI were not different between normotensive and hypertensive T2D patients (P Ͼ 0.05). Interestingly, MSNA responses were also greater in T2D patients compared with controls during the CPT (P Ͻ 0.05). Collectively, these findings indicate that muscle metaboreflex activation is augmented in T2D patients and this contributes, in part, to augmented pressor and sympathetic responses to exercise in this patient group. Greater CPT responses suggest that a heightened central sympathetic reactivity may be involved.exercise; hypertension; muscle sympathetic nerve activity; postexercise ischemia; blood pressure TYPE 2 DIABETES (T2D) patients exhibit exaggerated increases in arterial blood pressure (BP) during exercise (23,25,39,44).Augmented BP responses have been observed even during moderate-intensity handgrip (38), a level of isometric forearm muscle contraction that is equivalent to many activities of daily living such as opening jars, or carrying groceries. This is important because repeated surges in BP throughout the day have been related to increased cardiovascular risk (11, 37). Likewise, exaggerated increases in exercise BP are related to adverse cardiovascular and cerebrovascular events both during and after physical activity (19,27,33). Indeed, the incidence of cardiovascular and cerebrovascular events such as myocardial infarction and stroke are significantly elevated among T2D patients (5,26,28,57). An augmented pressor response to exercise is also a predictor for the development of hypertension (HTN) (10, 47), a common comorbidity amon...

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Enhanced metaboreflex sensitivity in hypertensive humans

Cited by 63 publications

References 29 publications

Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus?

Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus?

Exaggerated exercise pressor reflex in adults with moderately elevated systolic blood pressure: role of purinergic receptors

Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients

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