Muscle mechanoreflex overactivity in hypertension: A role for centrally-derived nitric oxide

Smith, Scott A.; Leal, Anna K.; Murphy, Megan N.; Downey, Ryan M.; Mizuno, Masaki

doi:10.1016/j.autneu.2014.12.004

Cited by 22 publications

(12 citation statements)

References 83 publications

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“…At the molecular level, two important factors associated with the overactive exercise pressor reflex in hypertension are the lower nitric oxide (NO) bioavailability and the greater oxidative stress mediated by angiotensin II (Smith et al . ; Thomas, ). NO modulates neural signalling in the nucleus tractus solitarius and rostral ventrolateral medulla, two areas related to autonomic and cardiovascular regulation.…”

Section: Discussionmentioning

confidence: 99%

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Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

Barbosa

Vianna

Fernandes

et al. 2016

The Journal of Physiology

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Key pointsr The increase in blood pressure observed during physical activities is exaggerated in patients with hypertension, exposing them to a higher cardiovascular risk.r Neural signals from the skeletal muscles appear to be overactive, resulting in this abnormal response in hypertensive patients.r In the present study, we tested whether the attenuation of these neural signals in hypertensive patients could normalize their abnormal increase in blood pressure during physical activity.r Attenuation of the neural signals from the leg muscles with intrathecal fentanyl injection reduced the blood pressure of hypertensive men during cycling exercise to a level comparable to that of normotensive men.r Skeletal muscle afferent overactivity causes the abnormal cardiovascular response to exercise and was reverted in this experimental model, appearing as potential target for treatment.Abstract Hypertensive patients present an exaggerated increase in blood pressure and an elevated cardiovascular risk during exercise. Although controversial, human studies suggest that group III and IV skeletal muscle afferents might contribute to this abnormal response. In the present study, we investigated whether attenuation of the group III and IV muscle afferent signal of hypertensive men eliminates the exaggerated increase in blood pressure occurring during exercise. Eight hypertensive men performed two sessions of 5 min of cycling exercise at 40 W. Between sessions, the subjects were provided with a lumbar intrathecal injection of fentanyl, a μ-opioid receptor agonist, aiming to attenuate the central projection of opioid-sensitive group III and IV muscle afferent nerves. The cardiovascular response to exercise of these subjects was compared with that of six normotensive men. During cycling, the hypertensive group demonstrated an exaggerated increase in blood pressure compared to the normotensive group (mean ± SEM: +17 ± 3 vs. +8 ± 1 mmHg, respectively; P < 0.05), whereas the increase in heart rate, stroke volume, cardiac output and vascular conductance was similar (P > 0.05). Fentanyl inhibited the blood pressure response to exercise in the hypertensive group (+11 ± 2 mmHg) to a level comparable to that of the normotensive group (P > 0.05). Moreover, fentanyl increased the responses of vascular conductance and stroke volume to exercise (P < 0.05), whereas the heart rate response was attenuated (P < 0.05) and the cardiac output response was maintained (P > 0.05). The results of the present study show that attenuation of the exercise pressor reflex normalizes the blood pressure response to cycling exercise in hypertensive individuals.

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Section: Discussionmentioning

confidence: 99%

“… a ; Smith et al . ), suggesting that NO bioavailability in the central nervous system may be decreased in hypertension. In this sense, oxidative enzymes activated by angiotensin II increase reactive oxygen species, such as superoxide anions.…”

Section: Discussionmentioning

confidence: 99%

Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

Barbosa

Vianna

Fernandes

et al. 2016

The Journal of Physiology

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“…Static (isometric) exercise causes heart rate-dependent increases in cardiac output accompanied by increased or unchanged peripheral vascular resistance resulting in substantially elevated BP [19,20]. 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].…”

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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“…As another example, sensory information generated by stimulation of the EPR is processed within the medulla oblongata. Within the medulla, the production of nitric oxide (NO) within the nucleus tractus solitarius (NTS), the site most critical for processing EPR sensory signals, buffers reflex-induced increases in SNA (56). It has been demonstrated that expression of neuronal NO synthase (NOS), necessary for the production of NO, is reduced throughout a large portion of the NTS in hypertensive rats (47).…”

Section: Possible Central Mechanisms Mediating Muscle Reflex Improvemmentioning

confidence: 99%

Dynamic exercise training prevents exercise pressor reflex overactivity in spontaneously hypertensive rats

Mizuno

Iwamoto

Vongpatanasin

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Mizuno M, Iwamoto GA, Vongpatanasin W, Mitchell JH, Smith SA. Dynamic exercise training prevents exercise pressor reflex overactivity in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 309: H762-H770, 2015. First published July 10, 2015; doi:10.1152/ajpheart.00358.2015.-Cardiovascular responses to exercise are exaggerated in hypertension. We previously demonstrated that this heightened cardiovascular response to exercise is mediated by an abnormal skeletal muscle exercise pressor reflex (EPR) with important contributions from its mechanically and chemically sensitive components. Exercise training attenuates exercise pressor reflex function in healthy subjects as well as in heart failure rats. However, whether exercise training has similar physiological benefits in hypertension remains to be elucidated. Thus we tested the hypothesis that the EPR overactivity manifest in hypertension is mitigated by exercise training. Changes in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in response to muscle contraction, passive muscle stretch, and hindlimb intra-arterial capsaicin administration were examined in untrained normotensive Wistar-Kyoto rats (WKY UT; n ϭ 6), exercise-trained WKY (WKYET; n ϭ 7), untrained spontaneously hypertensive rats (SHR UT; n ϭ 8), and exercise-trained SHR (SHRET; n ϭ 7). Baseline MAP after decerebration was significantly decreased by 3 mo of wheel running in SHR ET (104 Ϯ 9 mmHg) compared with SHR UT (125 Ϯ 10 mmHg). As previously reported, the pressor and renal sympathetic responses to muscle contraction, stretch, and capsaicin administration were significantly higher in SHR UT than WKYUT. Exercise training significantly attenuated the enhanced contraction-induced elevations in MAP (SHR UT: 53 Ϯ 11 mmHg; SHR ET: 19 Ϯ 3 mmHg) and RSNA (SHRUT: 145 Ϯ 32%; SHRET: 57 Ϯ 11%). Training produced similar attenuating effects in SHR during passive stretch and capsaicin administration. These data demonstrate that the abnormally exaggerated EPR function that develops in hypertensive rats is significantly diminished by exercise training. exercise pressor reflex; blood pressure; sympathetic nerve activity; hypertension; exercise training NEW & NOTEWORTHYThe study demonstrates that the exercise pressor reflex overactivity manifest in hypertension is attenuated by dynamic exercise training. Moreover, training normalizes the dysfunction of the mechanically and chemically sensitive components of the reflex. These findings identify a novel mechanism by which exercise training is beneficial in the treatment of hypertension.

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Muscle mechanoreflex overactivity in hypertension: A role for centrally-derived nitric oxide

Cited by 22 publications

References 83 publications

Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

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

Dynamic exercise training prevents exercise pressor reflex overactivity in spontaneously hypertensive rats

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