Influence of bicarbonate on the sensitivity of renin release to sodium chloride.
Juxtaglomerular cells in vitro are sensitive to changes in osmolality, but it is unknown whether volume-regulatory changes in cellular ion fluxes are important for the renin secretory process. The sensitivity of renin release to increases in osmolality by NaCl was therefore tested on superfused rat glomeruli treated with bicarbonate/chloride exchange inhibitor (DNDS), NaCl/KCl cotransport inhibitor (bumetanide), or Na+/H+ antiport inhibitor (amiloride) in the presence or absence of bicarbonate. In addition, the sensitivity to increases in osmolality by addition of sucrose was tested in the presence or absence of bicarbonate. Renin release from time controls superfused with a bicarbonate-free Ringer was identical to release from glomeruli superfused with a bicarbonate Ringer. DNDS (0.11 or 1.1 mM) had no effect on renin release in a bicarbonate Ringer. 30 mM sucrose inhibited renin release independently of bicarbonate. 15 mM NaCl stimulated renin release when bicarbonate was absent, while it caused an inhibition in the presence of bicarbonate. When bicarbonate/chloride exchange was inhibited, addition of NaCl stimulated renin release even when bicarbonate was present. The effect of NaCl on renin release was not affected by amiloride (1 mM) or bumetanide (10 microM). Thus, volume regulatory mechanisms as known from other cells are not involved in the renin secretory response to small increases in NaCl concentration. Furthermore, the sensitivity of renin release to changes in NaCl concentrations is modulated by bicarbonate in a way that depends on a functioning anion-exchange mechanism. The results are compatible with the existence in the membrane of the secretory granule of a Cl-/HCO3- exchange mechanism which mediates exit of Cl-, and thereby attenuates granular swelling and exocytotic release.
Skøtt
O
O
University Institute of Experimental Medicine, Panum Institute, Copenhagen, Denmark.
Jensen
B L
BL
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D006531:HEPES / Q000494:pharmacology; D066298:In Vitro Techniques; D007606:Juxtaglomerular Apparatus / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*; D012965:Sodium Chloride / Q000378:metabolism*
D001639:Bicarbonates; D012965:Sodium Chloride; D012083:Renin; D006531:HEPES