Cardiotonic steroids

AB - In response to progressive nephron loss, volume and humoral signals in the circulation have increasing relevance. These signals, including plasma sodium, angiotensin II, and those related to volume status, activate a slow neuromodulatory pathway within the central nervous system (CNS). The slow CNS pathway includes specific receptors for angiotensin II, mineralocorticoids, and endogenous ouabain (EO). Stimulation of the pathway leads to elevated sympathetic nervous system activity (SNA) and increased circulating EO. The sustained elevation of circulating EO (or ouabain) stimulates central and peripheral mechanisms that amplify the impact of SNA on vascular tone. These include changes in synaptic plasticity in the brain and sympathetic ganglia that increase preganglionic tone and amplify ganglionic transmission, amplification of the impact of SNA on arterial tone in the vascular wall, and the reprogramming of calcium signaling proteins in arterial myocytes. These increase SNA, raise basal and evoked arterial tone, and elevate blood pressure (BP). In the setting of CKD, we suggest that sustained activation/elevation of the slow CNS pathway, plasma EO, and the cardiotonic steroid marinobufagenin, comprises a feed-forward system that raises BP and accelerates kidney and cardiac damage. Block of the slow CNS pathway and/or circulating EO and marinobufagenin may reduce BP and slow the progression to ESRD.

In any case, many of the other points made by article are valid and helpful: sea salt shouldn’t be automatically assumed to be healthy, for example. Outside of trying to specifically attribute specific disease causes to sodium in general, or NaCl in particular, I think the demonstrated cellular effects are interesting and worth consideration, as they support the view that adding high salt/sodium could upset or change the milieu intérieur and that could have a whole host of undesirable effects and consequences. Let’s just not confuse that with anything close to a known, substantiated, direct causal effect.

Cardiotonic steroids

cardiotonic steroids


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