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    Baroreflex function is an integral component maintaining consistent blood pressure. Hypertension is often associated with baroreflex dysfunction, and environmental risk factors such as high salt diet exacerbate hypertension in subjects with baroreflex dysfunction. However, the interactions between high salt diet, baroreflex dysfunction, and hypertension are incompletely understood. The endothelin system is another potent mediator of blood pressure control especially in response to a high salt diet. We hypothesized that the endothelin B (ETB) receptor activation on adrenergic nerves decreases baroreflex sensitivity. We utilized male ETB receptor deficient (ETB-def) rats that express functional ETB receptors only on adrenergic nerves and transgenic (TG) controls to evaluate baroreflex function during normal (0.49% NaCl) and high (4.0% NaCl) salt diets. In conscious rats equipped with telemetry, ETB-def rats had an increased lability of systolic blood pressure (SBP) compared to TG controls as indicated by higher standard deviation (SD) of SBP under both normal (10.2 ± 0.6 vs. 12.4 ± 0.9 mmHg, respectively, p = 0.0001) and high (11.7 ± 0.6 vs. 16.1 ± 1.0 mmHg, p = 0.0001) salt diets. In anesthetized preparations, ETB-def rats displayed reduced heart rate (p genotype = 0.0167) and renal sympathetic nerve (p genotype = 0.0022) baroreflex sensitivity. We then gave male Sprague-Dawley rats the selective ETB receptor antagonist, A-192621 (10 mg/kg/day), to block ETB receptors. Following ETB receptor antagonism, even though SBP increased (131 ± 7 before vs. 152 ± 8 mmHg after, p < 0.0001), the lability (standard deviation) of SBP decreased (9.3 ± 2.0 vs. 7.1 ± 1.1 mmHg, p = 0.0155). These data support our hypothesis that ETB receptors on adrenergic nerves contribute to baroreflex dysfunction. Copyright © 2021 Elsevier B.V. All rights reserved.


    Bryan K Becker, Jermaine G Johnston, Carolyn M Young, Alfredo A Torres Rodriguez, Chunhua Jin, David M Pollock. Endothelin B receptors impair baroreflex function and increase blood pressure variability during high salt diet. Autonomic neuroscience : basic & clinical. 2021 May;232:102796

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    PMID: 33798837

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