Abstract

The present study was undertaken to further evaluate the interaction of adenosine and the renin angiotensin system. In 12 sodium-restricted (SR) Sprague-Dawley rats plasma renin activity in the arterial carotid (PRAa) and the renal venous (PRAv) blood was measured using a radioimmunoassay for angiotensin I (AI). Renin secretion rate (RS) was calculated from the arteriovenous difference of PRA and renal plasma flow obtained from the reading of an electromagnetic flowmeter and hematocrit. Adenosine infused into the thoracic aorta at a rate of 33 nmol/min·100g body weight, decreased RS from 250±29 ng AI/min in the control periods to 115±17 ng AI/min (P<0.001, n=9). After cessation of the adenosine infusion RS recovered incompletely to 167±21 ng/AI/min. Adenosine reduced glomerular filtration rate (GFR) by 56% (P<0.001) but renal blood flow (RBF) by only 20%. The effects of adenosine were also studied in a group of sodium loaded (SL) rats. In 6 non-laparotomized SL rats (PRAa=16±5 ng AI/ml·h) GFR was not significantly changed following adenosine infusion (1.54±0.16 vs 1.42±0.09 ml/min). In additional 7 SL rats (PRAa=39±4 ng AI/ml·h) in which RBF was measured with an electromagnetic flow probe, adenosine reduced GFR by 20% (P<0.01), whereas RBF increased from 13.7±1.2 to 16.5±2.2 ml/min (P<0.05). RS in SL rats was not affected by adenosine infusion (59±16 vs 62±26 ng AI/min). There was a close correlation between the adenosine induced decrease of GFR and PRAa (r=0.91, n=25) suggesting a higher sensitivity of the renal vasculature to adenosine when the renin-angiotensin system was stimulated. Micropuncture experiments in 9 Sprague-Dawley rats on a normal sodium diet demonstrated that adenosine infused in the low dose of 5 nmol/min·100 g of body weight markedly decreased the superficial nephron GFR from 38.6±2.65 to 20.5±1.67 nl/min (P<0.001) whereas whole kidney GFR was not changed significantly. This disproportionate response of superficial nephron compared to whole kidney GFR indicates that adenosine affects preferentially the superficial nephrons. It is concluded that adenosine depresses the renin secretion in SR rats. This depression was accompanied by a marked fall of the GFR. The renal response to adenosine was nearly abolished in SL rats suggesting that the renal action of adenosine is functionally related to the reninangiotensin system.

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