The role of endothelin A receptors in peripheral vascular control at rest and during exercise in patients with hypertension.
The role of endothelin A receptors in peripheral vascular control at rest and during exercise in patients with hypertension.
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DOI：
10.1113/jp279077
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发表时间：
2020-01
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影响因子：
--
通讯作者：
Trinity JD
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文献类型：
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作者：
Craig JC;Broxterman RM;La Salle DT;Cerbie J;Ratchford SM;Gifford JR;Bunsawat K;Nelson AD;Bledsoe AD;Morgan DE;Wray DW;Richardson RS;Trinity JD
高血压患者在运动过程中会表现出肌肉血流量受损和血压过度升高。虽然内皮素（ET）-1在健康人运动过程中对血流和血压起调节作用，但对ET-1在高血压患者运动心血管反应中的作用知之甚少。因此，8名被诊断患有高血压的志愿者在运动期间接受了生理盐水或BQ-123（ETA受体拮抗剂）输注，随后停用抗高血压药物2周。将股总动脉和静脉插管用于药物输注、血液收集和血压测量，并通过多普勒超声测量腿部血流。患者在绝对（0、5、10、15 W）和相对（40、60、80%峰值功率）强度下进行运动。BQ-123增加了静息时的血流量（79±87 ml/min; p=0.03），并在大多数强度下增强了运动诱导的充血（80%生理盐水：Δ3818±1222 vs BQ-123：Δ4812±1469 ml/min; p=0.001）。BQ-123降低静息时腿部MAP（-8 ±4 mmHg; p<0.001）和较低强度（0-10 W; p<0.05）。全身舒张压降低（0 W-40%; p<0.05），但全身MAP通过增加心输出量来保护。不同条件下的运动升压反应（ΔMAP）无差异（80%生理盐水：25±10，BQ-123：30±7 mmHg; p=0.17）。因此，ET-1通过ETA受体起作用，有助于控制这些患者在休息和低强度运动时的血压。此外，ET-1抑制血流对运动的反应的发现表明，ETA受体拮抗剂可能是一种治疗方法，以改善高血压运动期间的血流。
Patients with hypertension can exhibit impaired muscle blood flow and exaggerated increases in blood pressure during exercise. While endothelin (ET)-1 plays a role in regulating blood flow and pressure during exercise in health, little is known about the role of ET-1 in the cardiovascular response to exercise in hypertension. Therefore, eight volunteers diagnosed with hypertension were studied during exercise with either saline or BQ-123 (ETA receptor antagonist) infusion following a 2-week withdrawal of anti-hypertensive medications. The common femoral artery and vein were catheterized for drug infusion, blood collection, and blood pressure measurements and leg blood flow was measured by Doppler ultrasound. Patients exercised at both absolute (0, 5, 10, 15 W) and relative (40, 60, 80 % peak power) intensities. BQ-123 increased blood flow at rest (79±87 ml/min; p=0.03) and augmented the exercise-induced hyperemia at most intensities (80% Saline: Δ3818±1222 vs BQ-123: Δ4812±1469 ml/min; p=0.001). BQ-123 reduced leg MAP at rest (−8±4 mmHg; p<0.001) and lower intensities (0-10 W; p<0.05). Systemic diastolic blood pressure was reduced (0 W-40 %; p<0.05), but systemic MAP was defended by an increased cardiac output. The exercise pressor response (ΔMAP) did not differ between conditions (80% saline: 25±10, BQ-123: 30±7 mmHg; p=0.17). Thus, ET-1, acting through the ETA receptors, contributes to the control of blood pressure at rest and lower intensity exercise in these patients. Furthermore, the finding that ET-1 constrains the blood flow response to exercise suggests that ETA receptor antagonism could be a therapeutic approach to improve blood flow during exercise in hypertension.