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Renin Production and Release Associated with Cyclic ADPRibose‐ Mediated Signaling: Evidence from CD38 Gene Knockout Mice
Author(s) -
xiong jing,
Xia Min,
Boini Krishna,
Li Pin-Lan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.690.21
Subject(s) - endocrinology , medicine , plasma renin activity , chemistry , renin–angiotensin system , cd38 , kidney , renal function , biology , blood pressure , microbiology and biotechnology , stem cell , cd34
Despite extensive studies, the intracellular regulatory mechanism of renin production and release is still poorly understood. The present study was designed to test whether CD38‐ADP‐ribosylcyclase signaling pathway contributes to the regulation of renin production and release. We found that the expression of CD38 and the activity of ADP‐ribosyl cyclase to produce cyclic ADP‐ribose (cADPR) were nearly abolished in the kidney from CD38 −/− mice, indicating that CD38 gene is a major enzyme responsible for the generation of cADPR in vivo . Mice lacking CD38 gene showed increased plasma renin activity (PRA) in either conscious or anesthetized state (P<0.05). Low salt intake markedly increased, but high salt intake significantly decreased renin release in both CD38 +/+ and CD38 −/− mice. Compared to low salt intake, the decrease in PRA in response to high salt intake in CD38 −/− mice was much larger than CD38 +/+ mice. In acute experiments, isoprenaline infusion and renal perfusion pressure (RPP) reduction were used to test renin release in both mouse stains. It was demonstrated that PRA increased upon isoprenaline infusion in CD38 −/− mice by 3 folds compared to CD38 +/+ mice. Accompanied with such increase in PRA, glomerular filtration rate (GFR), renal blood flow (RBF), urine volume (UV) and sodium excretion (UNa) more significantly decreased in CD38 −/− than CD38 +/+ mice. Similarly, more increases in PRA but more decreases in GFR, RBF, UV and UNa were observed in CD38 −/− than CD38 +/+ mice when they had a low renal perfusion pressure (RPP). Finally, it was found that increase in RBF induced by intravenous injection of losartan (20 mg/kg) in CD38 −/− mice with high PRA was significantly attenuated compared to CD38 +/+ mice. In conclusion, the CD38‐cADPR‐mediated signaling may importantly contribute to the maintenance of low PRA and thereby participates in the regulation of renal hemodynamics and excretory function (Supported by NIH grants HL‐091464, HL‐75316 and DK54927).