Oral Administration of Amiloride Does Not Affect Spontaneous Cardiac Baroreflex Sensitivity in Humans

PHYSIOLOGY(2023)

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Abstract
Pre-clinical models suggested that administration of Amiloride at the carotid sinus antagonizes the acid-sensing ion channels (ASICS), an essential component of the mechanoelectrical transducer in the arterial baroreceptors, reducing cardiac baroreflex sensitivity and perturbing the homeostatic beat-to-beat blood pressure (BP) regulation. However, it is still undetermined whether these findings could be translated into humans. Therefore, we determined whether oral administration of Amiloride reduces the spontaneous cardiac baroreflex (cBRS) sensitivity and perturbs BP regulation in humans. Heart rate (HR; electrocardiography) and beat-to-beat BP (finger photoplethysmography) were continuously measured in 5 healthy men (32 ± 6 yrs) during at least 5 min in two different conditions: (1) Control (CTL) and (2) 3 h after of oral administration of Amiloride (AMD – 5 mg + 50 mg of hydrochlorothiazide), a non-selective antagonist of ASICs. Spontaneous cardiac BRS was determined for all sequences (three or more consecutive beats with corresponding increases or decreases in systolic BP and R-R interval) combined (cBRSall) and separately for up (cBRSup – increases in BP and R-R interval) and down (cBRSdown – decreases in BP and R-R interval) sequences. HR (AMD 65 ± 7 vs. CLT 63 ± 12 beats/min, P = 0.543), mean (AMD 88 ± 9 vs. CLT 88 ± 7 mmHg, P = 0.687), and systolic BP (AMD 126 ± 14 vs. 128 ± 11 mmHg, P = 0.717) were similar in both conditions. Likewise, spontaneous cBRSall (AMD 20 ± 9 vs. CTL 22 ± 6 ms/mmHg, P = 0.543), cBRSup (AMD 19 ± 10 vs. CTL 22 ± 6 ms/mmHg, P = 0.495,) and cBRSdown (AMD 21 ± 9 vs. CTL 21 ± 8 ms/mmHg, P = 0.937) were preserved after AMD administration. In summary, our preliminary results demonstrated that the non-selective antagonism of ASICS via oral administration of AMD did not affect spontaneous cardiac baroreflex sensitivity and BP regulation in humans. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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Key words
Baroreflex, blood pressure, heart rate
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