Exercise pressor reflex function is altered in spontaneously hypertensive rats

Smith, Scott A.; Williams, Maurice A.; Leal, Anna K.; Mitchell, Jere H.; Garry, Mary G.

doi:10.1113/jphysiol.2006.121558

Cited by 79 publications

(110 citation statements)

References 44 publications

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“…One was 30-s continuous static contraction, commonly used to study the physiological roles of the exercise pressor reflex (19,20,37,38,43). Another was 1-min intermittent (1-4 s of stimulation to relaxation) static contraction.…”

Section: H148mentioning

confidence: 99%

“…This muscle-based reflex is termed the exercise pressor reflex (35). A series of studies by Smith and colleagues (24,37,38,43) using a decerebrate rat preparation has suggested that in spontaneous hypertensive rats (SHRs), both mechanically and chemically sensitive muscle afferents engaged during skeletal muscle contraction are stimulated excessively compared with those in normotensive rats, thereby evoking exaggerated sympathoexcitatory and pressor responses to contraction. In humans with hypertension, the elevation in muscle sympathetic nerve activity seen during postexercise ischemia, a maneuver that selectively excites chemically sensitive muscle afferents, was higher than that in normotensive subjects (10).…”

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confidence: 99%

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Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II

Koba

Watanabe

Kano

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Koba S, Watanabe R, Kano N, Watanabe T. Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II. Am J Physiol Heart Circ Physiol 304: H142-H153, 2013. First published October 19, 2012 doi:10.1152/ajpheart.00423.2012.-Muscle contraction stimulates thin fiber muscle afferents and evokes reflex sympathoexcitation. In hypertension, this reflex is exaggerated. ANG II, which is elevated in hypertension, has been reported to trigger the production of superoxide and other reactive oxygen species. In the present study, we tested the hypothesis that increased ANG II in hypertension exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation by inducing oxidative stress in the muscle. In rats, subcutaneous infusion of ANG II at 450 ng·kg Ϫ1 ·min Ϫ1 for 14 days significantly (P Ͻ 0.05) elevated blood pressure compared with shamoperated (sham) rats. Electrically induced 30-s hindlimb muscle contraction in decerebrate rats with hypertension evoked larger renal sympathoexcitatory and pressor responses [ϩ1,173 Ϯ 212 arbitrary units (AU) and ϩ35 Ϯ 5 mmHg, n ϭ 10] compared with sham normotensive rats (ϩ419 Ϯ 103 AU and ϩ13 Ϯ 2 mmHg, n ϭ 11). Tempol, a SOD mimetic, injected intra-arterially into the hindlimb circulation significantly reduced responses in hypertensive rats, whereas this compound had no effect on responses in sham rats. Tiron, another SOD mimetic, also significantly reduced reflex renal sympathetic and pressor responses in a subset of hypertensive rats (n ϭ 10). Generation of muscle superoxide, as evaluated by dihydroethidium staining, was increased in hypertensive rats. RT-PCR and immunoblot experiments showed that mRNA and protein for gp91 phox , a NADPH oxidase subunit, in skeletal muscle tissue were upregulated in hypertensive rats. Taken together, hese results suggest that increased ANG II in hypertension induces oxidative stress in skeletal muscle, thereby exaggerating the muscle reflex. muscle contraction; angiotensin II; oxidative stress; sympathetic nerve activity HYPERTENSION is associated with an increased risk of cardiovascular disease (50). Antihypertensive treatments include increased physical activity or exercise (8, 23). It has been noted that in hypertension, the sympathoexcitation and elevation of blood pressure seen during exercise are excessive (10,39). This cardiovascular hyperexcitability is potentially dangerous because it can elevate risks for adverse cardiac events such as acute myocardial ischemia, myocardial infarction, left ventricular hypertrophy, or arrhythmia as well as stroke after a bout of exercise (23,36). Determining the causes underlying the hyperexcitability in this pathological condition is clinically important.A reflex originating in exercising skeletal muscle is activated as thin fiber muscle afferents (groups III and IV) are stimulated by mechanical deformation of the afferents' receptive fields as well as by metabolic byproducts during contraction (9, 33). In turn, afferent e...

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Section: H148mentioning

confidence: 99%

mentioning

confidence: 99%

Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II

Koba

Watanabe

Kano

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…4,18,19). Of these, recent evidence in both the animal and human literature suggests that the EPR contributes significantly to the abnormally accentuated circulatory response to exercise in hypertension (2,22,23,38). Activation of the EPR, a reflex originating in skeletal muscle, is mediated by stimulation of mechanically sensitive receptors located primarily on group III afferent fibers and metabolically sensitive receptors located primarily on group IV afferent fibers (10, 11).…”

mentioning

confidence: 99%

“…Activation of the EPR, a reflex originating in skeletal muscle, is mediated by stimulation of mechanically sensitive receptors located primarily on group III afferent fibers and metabolically sensitive receptors located primarily on group IV afferent fibers (10,11). In hypertension, combined or individual activation of either the mechanical (i.e., mechanoreflex) or metabolic component (i.e., metaboreflex) of the EPR results in a heightened sympathetically mediated cardiovascular response (2,13,22,23,34,38). To date, however, the mechanisms underlying EPR overactivity in hypertension remain largely unknown.…”

mentioning

confidence: 99%

Neuronal nitric oxide synthase expression is lower in areas of the nucleus tractus solitarius excited by skeletal muscle reflexes in hypertensive rats

Murphy

Mizuno²,

Downey

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Murphy MN, Mizuno M, Downey RM, Squiers JJ, Squiers KE, Smith SA. Neuronal nitric oxide synthase expression is lower in areas of the nucleus tractus solitarius excited by skeletal muscle reflexes in hypertensive rats. Am J Physiol Heart Circ Physiol 304: H1547-H1557, 2013. First published April 5, 2013; doi:10.1152/ajpheart.00235.2012.-The functions of the skeletal muscle exercise pressor reflex (EPR) and its mechanically sensitive component are augmented in hypertension producing exaggerated increases in blood pressure during exercise. Afferent information from the EPR is processed in the nucleus tractus solitarius (NTS). Within the NT, nitric oxide (NO), produced via L-arginine oxidation by neuronal nitric oxide synthase (nNOS), buffers the pressor response to EPR activation. Therefore, EPR overactivity may manifest as a decrease in NO production due to reductions in nNOS. We hypothesized that nNOS protein expression is lower in the NTS of spontaneously hypertensive (SHR) compared with normotensive Wistar-Kyoto (WKY) rats. Further, we examined whether nNOS is expressed with FOS, a marker of neuronal excitation induced by EPR activation. The EPR and mechanoreflex were intermittently activated for 1 h via hindlimb static contraction or stretch, respectively. These maneuvers produced significantly greater pressor responses in SHR during the first 25 min of stimulation. Within the NTS, nNOS expression was lower from Ϫ14.9 to Ϫ13.4 bregma in SHR compared with WKY. For example, at Ϫ14.5 bregma the number of NTS nNOS-positive cells in SHR (13 Ϯ 1) was significantly less than WKY (23 Ϯ 2). However, the number of FOS-positive cells after muscle contraction in this area was not different (WKY ϭ 82 Ϯ 18; SHR ϭ 75 Ϯ 8). In both groups, FOS-expressing neurons were located within the same areas of the NTS as neurons containing nNOS. These findings demonstrate that nNOS protein expression is lower within NTS areas excited by skeletal muscle reflexes in hypertensive rats.hypertension; exercise; nucleus tractus solitarius PHYSICAL ACTIVITY INDUCES increases in arterial blood pressure (ABP), heart rate (HR), and sympathetic nerve activity (20,32). In hypertension, exercise evokes abnormally exaggerated elevations in each of these variables (2, 9, 27). This places hypertensive patients at a greater risk for the occurrence of an adverse cardiovascular and/or cerebrovascular event during or immediately after a bout of exercise (6, 21). As a result, the intensity and duration of exercise prescription at a level that is both safe and therapeutically effective are often limited. Thus determining the cause of the cardiovascular hyperexcitability manifest in hypertension is clinically important.Exercise-induced autonomic changes in the cardiovascular system are mediated by the central command, the arterial baroreflex and the exercise pressor reflex (EPR; Refs. 4,18,19). Of these, recent evidence in both the animal and human literature suggests that the EPR contributes significantly to the abnormally accentuated circulatory response to ...

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“…First, Smith et al 84) showed that electrically induced continuous static muscle contraction reflexly elicited a greater pressor response in spontaneous hypertensive rats (SHRs) than that in normotensive controls, suggesting the exaggeration of the EPR in hypertension (Fig. 2).…”

Section: Contribution Of Rat Studies To Understanding Of Mechanisms Umentioning

confidence: 99%

Exercise pressor reflex in health and diseases: Animal studies

Koba

2015

JPFSM

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A reflex originating in exercising skeletal muscle contributes to sympathoexcitation during exercise. This muscle-based reflex is termed the exercise pressor reflex (EPR). In this review, mechanisms underlying activation of the EPR are examined based on findings mainly obtained from cat studies. Specifically, roles played by chemical and mechanical stimuli due to contraction in increasing discharges of muscle afferent fibers are discussed. Roles metabolic byproducts play in stimulating and sensitizing muscle afferents are also examined. Central cardiovascular sites involved in activation of the EPR are investigated. In this review, moreover, mechanisms by which the EPR function becomes abnormal in heart failure and hypertension are discussed on the basis of experimental data mainly provided by rat studies. In heart failure, the muscle metaboreflex is attenuated while the mechanoreflex is enhanced. In hypertension, both the muscle metabo-and mechano-reflexes are enhanced. Peripheral factors leading to EPR dysfunction in these pathological conditions are examined.

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Exercise pressor reflex function is altered in spontaneously hypertensive rats

Cited by 79 publications

References 44 publications

Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II

Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II

Neuronal nitric oxide synthase expression is lower in areas of the nucleus tractus solitarius excited by skeletal muscle reflexes in hypertensive rats

Exercise pressor reflex in health and diseases: Animal studies

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