Attenuated muscle metaboreflex-induced pressor response during postexercise muscle ischemia in renovascular hypertension

Abstract

DS. Attenuated muscle metaboreflex-induced pressor response during postexercise muscle ischemia in renovascular hypertension. Am J Physiol Regul Integr Comp Physiol 308: R650 -R658, 2015. First published January 28, 2015 doi:10.1152/ajpregu.00464.2014.-During dynamic exercise, muscle metaboreflex activation (MMA; induced via partial hindlimb ischemia) markedly increases mean arterial pressure (MAP), and MAP is sustained when the ischemia is maintained following the cessation of exercise (postexercise muscle ischemia, PEMI). We previously reported that the sustained pressor response during PEMI in normal individuals is driven by a sustained increase in cardiac output (CO) with no peripheral vasoconstriction. However, we have recently shown that the rise in CO with MMA is significantly blunted in hypertension (HTN). The mechanisms sustaining the pressor response during PEMI in HTN are unknown. In six chronically instrumented canines, hemodynamic responses were observed during rest, mild exercise (3.2 km/h), MMA, and PEMI in the same animals before and after the induction of HTN [Goldblatt two kidney, one clip (2K1C)]. In controls, MAP, CO and HR increased with MMA (ϩ52 Ϯ 6 mmHg, ϩ2.1 Ϯ 0.3 l/min, and ϩ37 Ϯ 7 beats per minute). After induction of HTN, MAP at rest increased from 97 Ϯ 3 to 130 Ϯ 4 mmHg, and the metaboreflex responses were markedly attenuated (ϩ32 Ϯ 5 mmHg, ϩ0.6 Ϯ 0.2 l/min, and ϩ11 Ϯ 3 bpm). During PEMI in HTN, HR and CO were not sustained, and MAP fell to normal recovery levels. We conclude that the attenuated metaboreflex-induced HR, CO, and MAP responses are not sustained during PEMI in HTN.exercise pressor reflex; postexercise circulatory occlusion; peripheral resistance; hypertension THE MUSCLE METABOREFLEX IS a very powerful blood pressureraising reflex (1,3,12,22,42,48,51,65). Metabolically sensitive afferents of this reflex (group III/IV) are stimulated by metabolites (e.g., protons, lactate, potassium, and diprotonated phosphate), which accumulate within underperfused active skeletal muscle (10, 19, 30, 32, 35, 46, 47, 56 -58, 61). Muscle metaboreflex activation results in a reflex increase in sympathetic outflow (9, 28 -30, 36 -38, 62). During submaximal dynamic exercise, metaboreflex activation markedly increases heart rate (HR), cardiac output (CO) and left ventricular dP/dt max , with little effect on the peripheral vasculature (5,16,17,26,27,55,60,65). Therefore, the substantial metaboreflex-mediated pressor response observed during mild dynamic exercise is virtually solely the result of the increase in CO.In contrast, when metaboreflex activation is maintained following the cessation of submaximal dynamic exercise (postexercise muscle ischemia, PEMI) in normal subjects, the pressor response is sustained despite a decrease in HR toward resting levels with a time course similar to normal recovery from exercise (1,2,21,44,49,50,(62)(63)(64). The fall in HR during PEMI led some investigators to question the role of CO in mediating the sustained pressor response during PEMI (21,49,50,63)....

Neural Control of Cardiovascular Function During Exercise in Hypertension

“…However, in heart failure (HF) this response appears to be abolished (Kaur et al, 2015b). In the study by Spranger et al (2015) the authors noted a hint of this shift in the mechanisms mediating the metaboreflex in the animals after induction of hypertension inasmuch as the small rise in peripheral vascular conductance during metaboreflex activation often noted in normal animals was abolished after induction of hypertension. This could indicate greater peripheral sympatho-activation during metaboreflex activation after induction of hypertension and/or reduced beta mediated vasodilation.…”

“…A study by Ranadive et al (2017) showed that there was no differences in muscle metaboreflex responses between women with a history of hypertensive pregnancies when compared to women that had normotensive pregnancies. Studies in conscious dogs concluded that metaboreflex-induced increases in MAP, cardiac output (CO), stroke volume (SV) and HR were reduced in dogs after induction of hypertension (Sala-Mercado et al, 2013) and that these attenuated responses were less sustained during PECO (Spranger et al, 2015). Previous studies in canines and humans have shown that when cardiac function is impaired the mechanisms mediating the metaboreflex pressor response during submaximal dynamic exercise “switch” from primarily increases in CO to primarily peripheral vasoconstriction (Hammond et al, 2000; Kim et al, 2005a; Crisafulli et al, 2011; Sala-Mercado et al, 2013).…”

“…When this restraint of coronary blood flow was blocked via prazosin, the increases in coronary blood flow and CO were restored toward normal. These data indicate that the primary reason for the attenuated metaboreflex responses seen in the canine studies was enhanced coronary vasoconstriction which limited increases in CO. Inasmuch as the rise in CO is the primary mechanism mediating the metaboreflex response when activated during exercise, when the cardiac component was decreased, the pressor response was likewise attenuated (Sala-Mercado et al, 2013; Spranger et al, 2015, 2017). Additionally, in HF previous studies have shown that muscle metaboreflex activation induces limitations in coronary blood flow resulting in a further reduced capacity to increase CO to match physiological demands (Kaur et al, 2015a).…”

Low‐intensity resistance exercise with blood flow restriction and arterial stiffness in humans: A systematic review

“…Also, neural signals from central command recruit motor units for muscle contraction and stimulate ACV regulation areas in the brainstem. The activation of sensitive skeletal muscle afferent neurons (metaboreflex and mechanoreflex) regulates the SMEPR that stimulates the brainstem areas 13 . Thus, sensory information to the central nervous system controls the efferent responses to the cardiovascular system.…”

“…Normally, LIRE‐BFR induces an increase in sympathetic nerve activity and decrease in parasympathetic nerve activity which are modulated by the arterial baroreflex 14 . Thus, these autonomic responses increase heart rate, cardiac output, cardiac contractility, and blood pressure 13 . As a result, these hemodynamic changes promote an elevation in arterial resistance and reduction in venous capacitance 15 …”