Effects of central sodium on epithelial sodium channels in rat brain.
We evaluated the effects of intracerebroventricular (icv) infusion of Na(+)-rich artificial cerebrospinal fluid (aCSF), with or without the mineralocorticoid receptor (MR) blocker spironolactone, on epithelial Na(+) channel (ENaC) subunits and regulators, such as MR, serum/glucocorticoid-inducible kinase 1, neural precursor cells expressed developmentally downregulated 4-like gene, 11beta-hydroxylase, and aldosterone synthase, in brain regions of Wistar rats. The effects of icv infusion of the amiloride analog benzamil on brain tissue and CSF Na(+) concentration ([Na(+)]) were also assessed. In the choroid plexus and ependyma of the anteroventral third ventricle, ENaC subunits are present in apical and basal membranes. Na(+)-rich aCSF increased beta-ENaC mRNA and immunoreactivity in the choroid plexus and increased alpha- and beta-ENaC immunoreactivities in the ependyma. Na(+)-rich aCSF increased alpha- and beta-ENaC-gold-labeled particles in the microvilli of the choroid plexus and in basolateral membranes of the ependyma. Spironolactone only prevented the increase in beta-ENaC immunoreactivity in the choroid plexus and ependyma. In the supraoptic nucleus, paraventricular nucleus, and subfornical organ, Na(+)-rich aCSF did not affect mRNA expression levels of the studied genes. Benzamil significantly increased CSF [Na(+)] in the control, but not Na(+)-rich, aCSF group. In contrast, benzamil prevented the increase in hypothalamic tissue [Na(+)] by Na(+)-rich aCSF. These results suggest that CSF Na(+) upregulates ENaC expression in the brain epithelia, but not in the neurons of hypothalamic nuclei. ENaC in the choroid plexus and ependyma appear to contribute to regulation of Na(+) homeostasis in the brain.
Wang
Hong-Wei
HW
Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Amin
Md Shahrier
MS
El-Shahat
Esraa
E
Huang
Bing S
BS
Tuana
Balwant S
BS
Leenen
Frans H H
FH
D000584:Amiloride / Q000031:analogs & derivatives; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid; D012964:Sodium / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000494:pharmacology; D012982:Sodium, Dietary / Q000494:pharmacology; D013148:Spironolactone / Q000378:metabolism / Q000494:pharmacology
D053503:Epithelial Sodium Channels; D005938:Glucocorticoids; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D012982:Sodium, Dietary; C038232:spironolactone receptor; C013407:benzamil; D013148:Spironolactone; D000584:Amiloride; D012964:Sodium; D019405:Cytochrome P-450 CYP11B2