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Regulation of N a + excretion and arterial blood pressure by purinergic signalling intrinsic to the distal nephron: consequences and mechanisms
Author(s) -
Mironova E.,
Boiko N.,
Bugaj V.,
Kucher V.,
Stockand J. D.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12372
Subject(s) - purinergic receptor , nephron , medicine , endocrinology , blood pressure , excretion , purinergic signalling , natriuresis , kidney , aldosterone , paracrine signalling , angiotensin ii , renin–angiotensin system , biology , chemistry , receptor , adenosine receptor , agonist
Discretionary control of Na + excretion is a key component of the regulation of arterial blood pressure in mammals. Sodium excretion is fine‐tuned in the aldosterone‐sensitive distal nephron by the activity of the epithelial Na + channel ( EN a C ). Here, EN a C functions as a final effector of the renin–angiotensin–aldosterone system ( RAAS ) during negative feedback control of blood pressure. Mutations affecting EN a C activity and abnormal regulation of this channel affect blood pressure through pathological changes to Na + excretion. Recent evidence demonstrates that powerful signalling pathways function in parallel with the RAAS to modulate EN a C activity and blood pressure. An inclusive paradigm is emerging with respect to regulation of blood pressure where EN a C serves as a critical point of convergence for several important signalling systems that affect renal Na + excretion. A robust inhibitory purinergic signalling system intrinsic to the distal nephron dynamically regulates EN a C through paracrine ATP signalling via the metabotropic P 2 Y 2 purinergic receptor to properly match urinary Na + excretion to dietary Na + intake. This enables blood pressure to be maintained within a normal range despite broad changes in dietary Na + consumption. Loss of purinergic inhibition of EN a C increases blood pressure by causing inappropriate Na + excretion. In contrast, stimulation of the P 2 Y 2 receptor promotes natriuresis and a decrease in blood pressure. Such observations identify purinergic signalling in the distal nephron as possibly causative, when dysfunctional, for certain forms of elevated blood pressure, and as a possible therapeutic target for the treatment of elevated blood pressure particularly that associated with salt sensitivity.