<p>The kidneys play a vital role in the maintenance of extracellular fluid and electrolyte balance and blood pressure. Adenosine, acting through the adenosine A<sub>1</sub>-receptor (A<sub>1</sub>R), and nitric oxide have been implicated in several of the regulatory mechanisms in the kidney. The A<sub>1</sub>R 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 A<sub>1</sub>R. Investigations on adenosine’s renal effects were performed on transgenic mice lacking the A<sub>1</sub>R.</p><p>TGF response, elicited by increased distal salt load, was completely abolished in the A1R knockout (A<sub>1</sub>R -/- ) mice. Basal plasma-renin levels were found to be ~2-fold higher in the A<sub>1</sub>R -/- compared to the A<sub>1</sub>R wild-type (A<sub>1</sub>R+/+) mice. However, salt intake induced inverse changes in plasma-renin levels, indicating that adenosine tonically inhibits macula densa stimulated renin release. Anesthetized and conscious A<sub>1</sub>R -/- 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 A<sub>1</sub>R -/- animals. Ischemia caused a decrease in renal function in both A<sub>1</sub>R+/+ and A<sub>1</sub>R -/- mice. Ischemic preconditioning protected the A<sub>1</sub>R+/+ mice from subsequent ischemic episode but had no protective effect on the A<sub>1</sub>R -/- mice.</p><p>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.</p><p>The results show that adenosine, acting through the A<sub>1</sub>R, plays an important role in mediating TGF response and consequently, regulating renin release, blood pressure, electrolyte balance and other vital renal mechanisms.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-4150 |
| Date | January 2004 |
| Creators | Brown, Russell |
| Publisher | Uppsala University, Physiology, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1339 |
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