Clinical Research Directory

EFFECT OF A SUBSTANCE P ANTAGONIST ON THE SECRETION OF ALDOSTERONE IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA SYNDROME AND ARTERIAL HYPERTENSION

Sponsor: University Hospital, Rouen

Summary

Obstructive sleep apnea syndrome (OSAS) is associated with hyperaldosteronism with elevated plasma aldosterone/renin ratio, the physiopathological mechanism of which remains uncertain. This hyperaldosteronism contributes to the development of arterial hypertension and cardiovascular complications observed in patients with OSA, in particular by increasing arterial stiffness and heart rate variability. The frequent association of OSA with obesity with metabolic syndrome suggests that excess weight could be responsible for stimulation of aldosterone secretion independent of the renin/angiotensin system. Several studies indicate in particular that the production of mineralocorticoids by the adrenals could be activated by various adipocyte secretion products such as leptin and certain fatty acids after oxidation in the liver. In addition, a recent study showed that basal aldosterone secretion is also controlled by substance P released within the adrenal tissue itself by nerve fibers belonging to the splanchnic contingent. Thus, the oral administration of aprepitant, an antagonist of the substance P receptor (NK1 receptor), to healthy volunteers induces a reduction of approximately 30% in the overall secretion of aldosterone assessed by measuring aldosteronemia and 24-hour aldosteronuria. To the extent that OSA causes sympathetic hypertonia, the hypothesis is that the associated hyperaldosteronism could result from activation of the nervous control of aldosterone secretion, involving substance P and the NK1 receptor. If this is indeed the case, the administration of aprepitant to patients with OSA should result in a significant reduction in aldosteronemia.

Official title: PILOT STUDY OF THE EFFECT OF A SUBSTANCE P ANTAGONIST, APREPITANT, ON THE SECRETION OF ALDOSTERONE IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA SYNDROME AND ARTERIAL HYPERTENSION

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