Spironolactone or Eplerenone Treatment Reduce the Exaggerated Pressor Response to Muscle Reflex Activation in Spontaneously Hypertensive Rats

Exercise is a beneficial treatment for hypertension. However, hypertensive patients frequently exhibit a dangerous, exaggerated rise in mean arterial pressure (MAP) during physical activity. Evidence suggests that the skeletal muscle exercise pressor reflex (EPR) plays a primary role in evoking this potentiated responsiveness, although the mechanisms remain largely undetermined. Studies suggest that mineralcorticoid receptors (MR) can contribute significantly to hypertension. Whether MR activation mediates EPR overactivity is unknown. Changes in MAP in response to EPR activation (via electrically‐induced hindlimb muscle contraction) were assessed in normotensive Wistar‐Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Additional SHR were fed (3 weeks) either normal chow (NC) or a customized diet containing the mineralcorticoid receptor antagonists spironolactone (SPIR, 50 mg/kg/day) or eplerenone (EPL, 100 mg/kg/day). The MAP response to EPR activation was markedly larger in SHR (37±8 mmHg) compared to WKY (9±2 mmHg). Further, the MAP response to EPR activation in SPIR‐treated and EPL‐treated SHR was much less than that elicited in SHR receiving NC (SPIR: 29±6, EPL: 31±5, NC: 42±7 mmHg/kg). These findings provide evidence that i) activation of MR mediates, in part, EPR overactivity in SHR and ii) SPIR and EPL may serve as viable treatments for EPR dysfunction in hypertension. Supported by NIH HL‐113738