Oppermann, Mona and Qin, Yan and Lai, En Yin and Eisner, Christoph and Li, Lingli and Huang, Yuning and Mizel, Diane and Fryc, Justyna and Wilcox, Christopher S. and Briggs, Josephine and Schnermann, Jurgen and Castrop, Hayo (2009) Enhanced tubuloglomerular feedback in mice with vascular overexpression of A(1) adenosine receptors. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 297 (5). F1256-F1264. ISSN 1931-857X,
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Oppermann M, Qin Y, Lai EY, Eisner C, Li L, Huang Y, Mizel D, Fryc J, Wilcox CS, Briggs J, Schnermann J, Castrop H. Enhanced tubuloglomerular feedback in mice with vascular overexpression of A(1) adenosine receptors. Am J Physiol Renal Physiol 297: F1256-F1264, 2009. First published September 9, 2009; doi: 10.1152/ajprenal.00264.2009.-Adenosine 1 receptors (A1AR) in the kidney are expressed in the vasculature and the tubular system. Pharmacological inhibition or global genetic deletion of A1AR causes marked reductions or abolishment of tubuloglomerular feedback (TGF) responses. To assess the function of vascular A1AR in TGF, we generated transgenic mouse lines in which A1AR expression in smooth muscle was augmented by placing A1AR under the control of a 5.38-kb fragment of the rat smooth muscle alpha-actin promoter and first intron (12). Two founder lines with highest expression in the kidney [353 +/- 42 and 575 +/- 43% compared with the wild type (WT)] were used in the experiments. Enhanced expression of A1AR at the expected site in these lines was confirmed by augmented constrictor responses of isolated afferent arterioles to administration of the A1AR agonist N-6-cyclohexyladenosine. Maximum TGF responses (0-30 nl/min flow step) were increased from 8.4 +/- 0.9 mmHg in WT (n = 21) to 14.2 +/- 0.7 mmHg in A1AR-transgene (tg) 4 (n = 22; P < 0.0001), and to 12.6 +/- 1.2 mmHg in A1AR-tg7 (n = 12; P < 0.02). Stepwise changes in perfusion flow caused greater numerical TGF responses in A1AR-tg than WT in all flow ranges with differences reaching levels of significance in the intermediate flow ranges of 7.5-10 and 10-15 nl/min. Proximal-distal single-nephron glomerular filtration rate (SNGFR) differences (free-flow micropuncture) were also increased in A1AR-tg, averaging 6.25 +/- 1.5 nl/min compared with 2.6 +/- 0.51 nl/min in WT (P = 0.034). Basal plasma renin concentrations as well as the suppression of renin secretion after volume expansion were similar in A1AR-tg and WT mice, suggesting lack of transgene expression in juxtaglomerular cells. These data indicate that A1AR expression in vascular smooth muscle cells is a critical component for TGF signaling and that changes in renal vascular A1AR expression may determine the magnitude of TGF responses.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLOMERULAR-FILTRATION RATE; RAT-KIDNEY; GENE-EXPRESSION; DEPENDENT INHIBITION; AFFERENT ARTERIOLES; RENIN SECRETION; A(2A) RECEPTORS; DEFICIENT MICE; MESSENGER-RNA; MOUSE STRAIN; single nephron glomerular filtration rate; smooth muscle; juxtaglomerular apparatus |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Wolf Hayo Castrop |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Sep 2020 06:31 |
| Last Modified: | 02 Sep 2020 06:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28159 |
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