Key result
Increases in macula densa NaCl concentration concurrently activate tubuloglomerular feedback and inhibit renin secretion, likely sharing common cellular mechanisms such as intracellular calcium changes.
This review highlights shared cellular mechanisms in the macula densa's regulation of glomerular vascular tone and renin secretion, providing insight into renal physiology.
Macula densa NaCl sensing integrates vascular and endocrine control; leaves open whether targeting shared calcium pathways alters clinical outcomes in hypertension or CKD.
The macula densa is believed to function as a sensor for control of intrarenal vascular tone and renin secretion. Increases in flow rate through the loop of Henle or increases in distal tubular fluid NaCl concentration result in an increase in local vascular tone and a decrease in glomerular filtration rate, the tubuloglomerular feedback (TGF) mechanism. Increases in distal NaCl concentration are also believed to inhibit renin secretion. Evidence will be reviewed that suggests that these two processes may be activated concurrently and may share common cellular mechanisms. Similarities in the sensor step include a similar pattern of ion specificity, with both responses being relatively anion specific but showing little cation specificity. TGF responses are inhibitable by furosemide, and the renin secretion produced by furosemide seems to be in part macula densa dependent. There appear also to be common features in the effector step of both responses. Increases in intracellular calcium are implicated in both the vasoconstrictive response seen with increased macula densa NaCl concentration and in inhibition of renin secretion. Changes in cyclic AMP may play a role in the converse responses.
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Briggs et al. (1986) conducted a review in Regulation of renin secretion and glomerular vascular tone. Macula densa NaCl concentration was evaluated. Increases in macula densa NaCl concentration concurrently activate tubuloglomerular feedback and inhibit renin secretion, likely sharing common cellular mechanisms such as intracellular calcium changes.
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