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Abolished Tubuloglomerular Feedback and Increased Plasma Renin in Adenosine A1-receptor Deficient Mice
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Physiology.
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2001 In: Am J Physiol Regulatory Integrative Comp Physiol, no 281, R1362-67 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2001. no 281, R1362-67 p.
URN: urn:nbn:se:uu:diva-91578OAI: oai:DiVA.org:uu-91578DiVA: diva2:164356
Available from: 2004-04-14 Created: 2004-04-14Bibliographically approved
In thesis
1. The Influence of the Adenosine A1-receptor on Tubuloglomerular Feedback and Renin Release
Open this publication in new window or tab >>The Influence of the Adenosine A1-receptor on Tubuloglomerular Feedback and Renin Release
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The kidneys play a vital role in the maintenance of extracellular fluid and electrolyte balance and blood pressure. Adenosine, acting through the adenosine A1-receptor (A1R), and nitric oxide have been implicated in several of the regulatory mechanisms in the kidney. The A1R has been found to be present in the renal vasculature, primarily in the afferent arterioles, and in the proximal tubules. The tubuloglomerular feedback mechanism (TGF) is an important regulator of renal vascular tone and glomerular filtration rate. The aim of these investigations was to further elucidate the role of adenosine, acting through the A1R. Investigations on adenosine’s renal effects were performed on transgenic mice lacking the A1R.

TGF response, elicited by increased distal salt load, was completely abolished in the A1R knockout (A1R -/- ) mice. Basal plasma-renin levels were found to be ~2-fold higher in the A1R -/- compared to the A1R wild-type (A1R+/+) mice. However, salt intake induced inverse changes in plasma-renin levels, indicating that adenosine tonically inhibits macula densa stimulated renin release. Anesthetized and conscious A1R -/- mice, measured telemetrically, had an increased blood pressure, which could be due to the increased plasma-renin levels. Despite the high plasma-renin levels, increased urinary sodium excretion was also observed in the A1R -/- animals. Ischemia caused a decrease in renal function in both A1R+/+ and A1R -/- mice. Ischemic preconditioning protected the A1R+/+ mice from subsequent ischemic episode but had no protective effect on the A1R -/- mice.

Acute extracellular volume expansion greatly attenuates TGF sensitivity, thus facilitating the elimination of excess fluid. Acute inhibition of nNOS in volume-expanded rats was found to re-establish the attenuated TGF response caused by acute extracellular volume expansion.

The results show that adenosine, acting through the A1R, plays an important role in mediating TGF response and consequently, regulating renin release, blood pressure, electrolyte balance and other vital renal mechanisms.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 54 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1339
Physiology, adenosine, tubuloglomerular feedback, renin release, blood pressure, micropuncture, Fysiologi
National Category
urn:nbn:se:uu:diva-4150 (URN)91-554-5929-3 (ISBN)
Public defence
2004-05-08, IV, Universtitetshuset, Uppsala, 13:15
Available from: 2004-04-14 Created: 2004-04-14Bibliographically approved

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