Hamlyn John M
Department of Physiology, University of Maryland School of Medicine , Baltimore, MD , USA.
Front Endocrinol (Lausanne). 2014 Dec 3;5:199. doi: 10.3389/fendo.2014.00199. eCollection 2014.
The work of deWardener and colleagues stimulated longstanding interest in natriuretic hormones (NHs). In addition to the atrial peptides (APs), the circulation contains unidentified physiologically relevant NHs. One NH is controlled by the central nervous system (CNS) and likely secreted by the pituitary. Its circulating activity is modulated by salt intake and the prevailing sodium concentration of the blood and intracerebroventricular fluid, and contributes to postprandial and dehydration natriuresis. The other NH, mobilized by atrial stretch, promotes natriuresis by increasing the production of intrarenal dopamine and/or nitric oxide (NO). Both NHs have short (<35 min) circulating half lives, depress renotubular sodium transport, and neither requires the renal nerves. The search for NHs led to endogenous cardiotonic steroids (CTS) including ouabain-, digoxin-, and bufadienolide-like materials. These CTS, given acutely in high nanomole to micromole amounts into the general or renal circulations, inhibit sodium pumps and are natriuretic. Among these CTS, only bufalin is cleared sufficiently rapidly to qualify for an NH-like role. Ouabain-like CTS are cleared slowly, and when given chronically in low daily nanomole amounts, promote sodium retention, augment arterial myogenic tone, reduce renal blood flow and glomerular filtration, suppress NO in the renal vasa recta, and increase sympathetic nerve activity and blood pressure. Moreover, lowering total body sodium raises circulating endogenous ouabain. Thus, ouabain-like CTS have physiological actions that, like aldosterone, support renal sodium retention and blood pressure. In conclusion, the mammalian circulation contains two non-AP NHs. Identification of the CNS NH should be a priority.
德瓦德纳及其同事的研究激发了人们对利钠激素（NHs）长期以来的兴趣。除了心房肽（APs）外，循环系统中还存在尚未明确的具有生理相关性的NHs。一种NH受中枢神经系统（CNS）控制，可能由垂体分泌。其循环活性受盐摄入量以及血液和脑室内液中钠浓度的影响，并有助于餐后和脱水利尿。另一种NH由心房牵张激活，通过增加肾内多巴胺和/或一氧化氮（NO）的生成来促进利尿。两种NH的循环半衰期都很短（<35分钟），抑制肾小管钠转运，且都不需要肾神经参与。对NHs的研究导致了内源性强心甾体（CTS）的发现，包括哇巴因、地高辛和蟾蜍二烯羟酸内酯样物质。这些CTS以高纳摩尔至微摩尔的剂量急性注入全身或肾循环时，会抑制钠泵并具有利尿作用。在这些CTS中，只有蟾毒灵清除速度足够快，符合类似NH的作用。哇巴因样CTS清除缓慢，当以每日低纳摩尔剂量长期给药时，会促进钠潴留，增强动脉肌源性张力，减少肾血流量和肾小球滤过，抑制肾直小血管中的NO，并增加交感神经活性和血压。此外，降低全身钠含量会提高循环中的内源性哇巴因水平。因此，哇巴因样CTS具有与醛固酮类似的生理作用，支持肾钠潴留和血压升高。总之，哺乳动物循环系统中存在两种非AP NHs。确定中枢神经系统NH应作为首要任务。
