Exaggerated sympathetic and pressor responses to handgrip exercise in older hypertensive humans: role of the muscle metaboreflex

Abstract

Recent animal studies have reported that exercise pressor reflex (EPR)-mediated increases in blood pressure are exaggerated in hypertensive (HTN) rodents. Whether these findings can be extended to human hypertension remains unclear. Mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and venous metabolites were measured in normotensive (NTN; n = 23; 60 ± 1 yr) and HTN (n = 15; 63 ± 1 yr) subjects at baseline, and during static handgrip at 30 and 40% maximal voluntary contraction (MVC) followed by a period of postexercise ischemia (PEI) to isolate the metabolic component of the EPR. Changes in MAP from baseline were augmented in HTN subjects during both 30 and 40% MVC handgrip (P < 0.05 for both), and these group differences were maintained during PEI (30% PEI trial: Δ15 ± 2 NTN vs. Δ19 ± 2 HTN mmHg; 40% PEI trial: Δ16 ± 1 NTN vs. Δ23 ± 2 HTN mmHg; P < 0.05 for both). Similarly, in HTN subjects, MSNA burst frequency was greater during 30 and 40% MVC handgrip (P < 0.05 for both), and these differences were maintained during PEI [30% PEI trial: 35 ± 2 (NTN) vs. 44 ± 2 (HTN) bursts/min; 40% PEI trial: 36 ± 2 (NTN) vs. 48 ± 2 (HTN) bursts/min; P < 0.05 for both]. No group differences in metabolites were observed. MAP and MSNA responses to a cold pressor test were not different between groups, suggesting no group differences in generalized sympathetic responsiveness. In summary, compared with NTN subjects, HTN adults exhibit exaggerated sympathetic and pressor responses to handgrip exercise that are maintained during PEI, indicating that activation of the metabolic component of the EPR is augmented in older HTN humans.

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

“…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].…”

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

“…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). These rodent and human studies suggest that the skeletal muscle contractionmediated reflex sympathetic nerve response is exaggerated in hypertension, thereby contributing to the excess sympathoexcitation and blood pressure elevation seen during exercise in this pathological condition.…”

“…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).…”

Exercise pressor reflex in health and diseases: Animal studies

“…While antihypertensive treatments include increased physical activity or exercise, we need to note that sympathoexcitatory and pressor responses to a bout of exercise are exaggerated in hypertension 83) . Cardiovascular hyperexcitability is a possible cause of adverse cardiac events such as acute myocardial ischemia, myocardial infarction, left ventricular hypertrophy, or arrhythmia as well as stroke.…”

“…Cardiovascular hyperexcitability is a possible cause of adverse cardiac events such as acute myocardial ischemia, myocardial infarction, left ventricular hypertrophy, or arrhythmia as well as stroke. Human studies have revealed that in hypertension the EPR function becomes abnormal 83) , thereby contributing to the cardiovascular hyperactivity. Mechanisms underlying the EPR dysfunction in hypertension have been investigated in rodent studies.…”