Department of Physiology and Biophysics, University of Mississippi Medical Center , Jackson, Mississippi.
John D. Bower School of Population Health, University of Mississippi Medical Center , Jackson, Mississippi.
Am J Physiol Heart Circ Physiol. 2018 Nov 1;315(5):H1368-H1382. doi: 10.1152/ajpheart.00302.2018. Epub 2018 Jul 13.
Electrical stimulation of the baroreflex chronically suppresses sympathetic activity and arterial pressure and is currently being evaluated for the treatment of resistant hypertension. The antihypertensive effects of baroreflex activation are often attributed to renal sympathoinhibition. However, baroreflex activation also decreases heart rate, and robust blood pressure lowering occurs even after renal denervation. Because controlling renal sympathetic nerve activity (RSNA) and cardiac autonomic activity cannot be achieved experimentally, we used an established mathematical model of human physiology (HumMod) to provide mechanistic insights into their relative and combined contributions to the cardiovascular responses during baroreflex activation. Three-week responses to baroreflex activation closely mimicked experimental observations in dogs including decreases in blood pressure, heart rate, and plasma norepinephrine and increases in plasma atrial natriuretic peptide (ANP), providing validation of the model. Simulations showed that baroreflex-induced alterations in cardiac sympathetic and parasympathetic activity lead to a sustained depression of cardiac function and increased secretion of ANP. Increased ANP and suppression of RSNA both enhanced renal excretory function and accounted for most of the chronic blood pressure lowering during baroreflex activation. However, when suppression of RSNA was blocked, the blood pressure response to baroreflex activation was not appreciably impaired due to inordinate fluid accumulation and further increases in atrial pressure and ANP secretion. These simulations provide a mechanistic understanding of experimental and clinical observations showing that baroreflex activation effectively lowers blood pressure in subjects with previous renal denervation. NEW & NOTEWORTHY Both experimental and clinical studies have shown that the presence of renal nerves is not an obligate requirement for sustained reductions in blood pressure during chronic electrical stimulation of the carotid baroreflex. Simulations using HumMod, a mathematical model of integrative human physiology, indicated that both increased secretion of atrial natriuretic peptide and suppressed renal sympathetic nerve activity play key roles in mediating long-term reductions in blood pressure during chronic baroreflex activation.
电刺激压力反射会长期抑制交感神经活动和动脉血压，目前正在评估其治疗难治性高血压的效果。压力反射激活的降压作用通常归因于肾交感神经抑制。然而，压力反射激活也会降低心率，即使在肾去神经支配后，也会出现强烈的血压降低。由于无法在实验中控制肾交感神经活动 (RSNA) 和心脏自主神经活动，我们使用已建立的人体生理学数学模型 (HumMod) 来提供对压力反射激活期间心血管反应的相对和综合贡献的机制见解。对压力反射激活的三星期反应与犬类的实验观察非常相似，包括血压、心率和血浆去甲肾上腺素降低，以及血浆心房利钠肽 (ANP) 增加，从而验证了该模型。模拟表明，压力反射引起的心脏交感和副交感神经活动的改变导致心脏功能持续抑制和 ANP 分泌增加。增加的 ANP 和 RSNA 的抑制均增强了肾脏排泄功能，并解释了压力反射激活期间大部分慢性血压降低的原因。然而，当抑制 RSNA 时，由于不适当的液体积累和心房压力和 ANP 分泌的进一步增加，对压力反射激活的血压反应并没有明显受损。这些模拟提供了对实验和临床观察的机制理解，表明即使在先前进行了肾去神经支配的情况下，压力反射激活也能有效地降低血压。新观点和值得注意的是，实验和临床研究均表明，在慢性电刺激颈动脉压力反射期间，肾神经的存在并不是血压持续降低的必需条件。使用 HumMod（一种综合人体生理学的数学模型）进行的模拟表明，心房利钠肽的分泌增加和肾交感神经活动的抑制均在介导慢性压力反射激活期间的长期血压降低中发挥关键作用。
