TY - JOUR
T1 - Mineralocorticoid receptor antagonists attenuate exaggerated exercise pressor reflex responses in hypertensive rats
AU - Downey, Ryan M.
AU - Mizuno, Masaki
AU - Mitchell, Jere H.
AU - Vongpatanasin, Wanpen
AU - Smith, Scott A.
N1 - Publisher Copyright:
© 2017 the American Physiological Society.
PY - 2017/10/11
Y1 - 2017/10/11
N2 - Exaggerated heart rate (HR) and blood pressure responses to exercise in hypertension are mediated, in part, by overactivity of the exercise pressor reflex (EPR). The mechanisms underlying this EPR dysfunction have not been fully elucidated. Previous studies have shown that stimulation of mineralocorticoid receptors (MRs) with exogenous administration of aldosterone in normal, healthy rats reproduces the EPR overactivity characteristic of hypertensive animals. Conversely, the purpose of this study was to examine whether antagonizing MR with spironolactone (SPIR) or eplerenone (EPL) in decerebrated hypertensive rats ameliorates abnormal EPR function. Changes in mean arterial pressure (MAP) and HR induced by EPR or muscle mechanoreflex (a component of EPR) activation were assessed in normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) fed normal chow (NC) or a customized diet containing either SPIR or EPL for 3 wk. SHRs treated with SPIR or EPL had significantly attenuated MAP responses to EPR (NC: 45 ± 7 mmHg, SPIR: 26 ± 4 mmHg, and EPL: 24 ± 5 mmHg, P = 0.02) and mechanoreflex (NC: 34 ± 9 mmHg, SPIR: 17 ± 3 mmHg, and EPL: 15 ± 3 mmHg, P = 0.03) activation. SHRs treated with SPIR or EPL also showed significantly attenuated HR responses to EPR (NC: 17 ± 3 beats/min, SPIR: 9 ± 1 beats/min, and EPL: 9 ± 2 beats/min, P = 0.01) and mechanoreflex (NC: 15 ± 3 beats/ min, SPIR: 6 ± 1 beats/min, and EPL: 7 ± 1 beats/min, P = 0.01) activation. Wistar-Kyoto rats treated with SPIR did not demonstrate significant differences in MAP or HR responses to EPR or mechanoreflex activation. The data suggest that antagonizing MRs may be an effective strategy for the treatment of EPR overactivity in hypertension.
AB - Exaggerated heart rate (HR) and blood pressure responses to exercise in hypertension are mediated, in part, by overactivity of the exercise pressor reflex (EPR). The mechanisms underlying this EPR dysfunction have not been fully elucidated. Previous studies have shown that stimulation of mineralocorticoid receptors (MRs) with exogenous administration of aldosterone in normal, healthy rats reproduces the EPR overactivity characteristic of hypertensive animals. Conversely, the purpose of this study was to examine whether antagonizing MR with spironolactone (SPIR) or eplerenone (EPL) in decerebrated hypertensive rats ameliorates abnormal EPR function. Changes in mean arterial pressure (MAP) and HR induced by EPR or muscle mechanoreflex (a component of EPR) activation were assessed in normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) fed normal chow (NC) or a customized diet containing either SPIR or EPL for 3 wk. SHRs treated with SPIR or EPL had significantly attenuated MAP responses to EPR (NC: 45 ± 7 mmHg, SPIR: 26 ± 4 mmHg, and EPL: 24 ± 5 mmHg, P = 0.02) and mechanoreflex (NC: 34 ± 9 mmHg, SPIR: 17 ± 3 mmHg, and EPL: 15 ± 3 mmHg, P = 0.03) activation. SHRs treated with SPIR or EPL also showed significantly attenuated HR responses to EPR (NC: 17 ± 3 beats/min, SPIR: 9 ± 1 beats/min, and EPL: 9 ± 2 beats/min, P = 0.01) and mechanoreflex (NC: 15 ± 3 beats/ min, SPIR: 6 ± 1 beats/min, and EPL: 7 ± 1 beats/min, P = 0.01) activation. Wistar-Kyoto rats treated with SPIR did not demonstrate significant differences in MAP or HR responses to EPR or mechanoreflex activation. The data suggest that antagonizing MRs may be an effective strategy for the treatment of EPR overactivity in hypertension.
KW - Aldosterone
KW - Blood pressure
KW - Eplerenone
KW - Heart rate
KW - Mechanoreflex
KW - Muscle reflexes
KW - Spironolactone
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U2 - 10.1152/ajpheart.00155.2017
DO - 10.1152/ajpheart.00155.2017
M3 - Article
C2 - 28733447
AN - SCOPUS:85031092750
SN - 0363-6135
VL - 313
SP - 788
EP - 794
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 4
ER -