Evidence for functional alterations in the skeletal muscle mechanoreflex and metaboreflex in hypertensive rats

Abstract

Leal AK, Williams MA, Garry MG, Mitchell JH, Smith SA. Evidence for functional alterations in the skeletal muscle mechanoreflex and metaboreflex in hypertensive rats. Am J Physiol Heart Circ Physiol 295: H1429 -H1438, 2008. First published July 18, 2008 doi:10.1152/ajpheart.01365.2007.-Exercise in hypertensive individuals elicits exaggerated increases in mean arterial pressure (MAP) and heart rate (HR) that potentially enhance the risk for adverse cardiac events or stroke. Evidence suggests that exercise pressor reflex function (EPR; a reflex originating in skeletal muscle) is exaggerated in this disease and contributes significantly to the potentiated cardiovascular responsiveness. However, the mechanism of EPR overactivity in hypertension remains unclear. EPR function is mediated by the muscle mechanoreflex (activated by stimulation of mechanically sensitive afferent fibers) and metaboreflex (activated by stimulation of chemically sensitive afferent fibers). Therefore, we hypothesized the enhanced cardiovascular response mediated by the EPR in hypertension is due to functional alterations in the muscle mechanoreflex and metaboreflex. To test this hypothesis, mechanically and chemically sensitive afferent fibers were selectively activated in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) decerebrate rats. Activation of mechanically sensitive fibers by passively stretching hindlimb muscle induced significantly greater increases in MAP and HR in SHR than WKY over a wide range of stimulus intensities. Activation of chemically sensitive fibers by administering capsaicin (0.01-1.00 g/100 l) into the hindlimb arterial supply induced increases in MAP that were significantly greater in SHR compared with WKY. However, HR responses to capsaicin were not different between the two groups at any dose. This data is consistent with the concept that the abnormal EPR control of MAP described previously in hypertension is mediated by both mechanoreflex and metaboreflex overactivity. In contrast, the previously reported alterations in the EPR control of HR in hypertension may be principally due to overactivity of the mechanically sensitive component of the reflex. blood pressure; heart rate; muscle afferents THE CARDIOVASCULAR RESPONSE to exercise is exaggerated in hypertension and is characterized by augmented increases in heart rate (HR), arterial blood pressure (ABP), and vascular resistance (3,15,19,25,38,43). These abnormal hemodynamic responses to physical activity in hypertension are associated with an increased risk for adverse cardiovascular events during and after exercise such as myocardial ischemia or infarction, cardiac arrest, and stroke (13,21,35,36). Therefore, dissection of the regulatory mechanisms underlying the altered hemodynamic responses to exercise in hypertension is important and clinically relevant.The cardiovascular response to exercise is mediated by three neurophysiological mechanisms: the exercise pressor reflex (EPR), central command, and the arterial baroreflex. The EPR is a ...

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

“…Based on the present results, we suggest that increased RAAS activity in hypertension sensitizes mechanically sensitive muscle afferents responding to contraction by inducing oxidative stress in the muscle. Mechanosensitive muscle afferent sensitization in hypertension has been suggested by the previous SHR studies reporting that RSNA and cardiovascular responses to stretch of the Achilles tendon, a maneuver that selectively excites mechanically sensitive muscle afferents, were excess in SHRs (24,37), and that the exaggerated responses to continuous contraction of hindlimb skeletal muscle in SHRs were reduced to a large degree (about half) by intra-arterial injection into the hindlimb circulation of gadolinium, a mechanoreceptor blocker (15,37).…”

“…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).…”

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

“…The rationale for these additional experiments was that 1) stimulation of mechanically sensitive afferent fibers can be readily induced by stretching skeletal muscle lending itself to a 30-s "stimulation/relaxation" protocol, and 2) the mechanoreflex component of the EPR has recently been shown to be dysfunctional in hypertension, producing elevated increases in ABP and sympathetic nerve activity (13,23). In a separate group of animals (WKY n ϭ 10; SHR n ϭ 11) than those in which muscle contraction was evoked, mechanically sensitive afferent fibers were preferentially stimulated by passively stretching the soleus and gastrocnemius muscles of the right hindlimb using a calibrated 9.5-mm rack and pinion system (Harvard Apparatus).…”

“…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.…”

Exercise pressor reflex in health and diseases: Animal studies

“…2). Then, Leal et al 85) showed that pressor responses to either passive muscle stretch or intra-arterial infusion of capsaicin into hindlimb circulation were greater in SHR, suggesting that the exaggerated EPR in hypertension is mediated by both mechanoreflex and metaboreflex overactivity (Fig. 2).…”