RENAL EFFECTS OF LOCAL INFUSION OF ADENOSINE IN MAN

1. The effects of local intra-arterial infusion of adenosine on renal blood flow, glomerular filtration and renin release in eight healthy a wake subjects have been examined. 2. Renal blood flow and glomerular f iltration rate were measured as the clearances of p-aminohippurate and inulin, respectively. After basal samplings, adenosine was infused in tra-arterially at successive rates of 2 and 10 mu g min(-1) kg(-1) for 40 min at each rate. 3. Apart from a small increase in heart rate (65 +/- 4 to 71 +/- 4 beats/min), there were no signs of sympathetic acti vation (unchanged blood pressure and catecholamine levels) during the infusion. Clearance of p-aminohippurate tended to increase, but not si gnificantly, during adenosine infusion (518 +/- 48 ml/min basal, 563 /- 52 ml/min during the highest dose of adenosine). The arterial plasm a concentration of p-aminohippurate decreased by 9 +/- 3% (P < 0.05), consistent with a small increase in renal blood flow in the infused ki dney. Inulin clearance was reduced from 115 +/- 3 to 97 +/- 2 ml/min ( P < 0.001). The extraction of inulin, reflecting the filtration fracti on, was 18% in both kidneys in the basal state. During infusion of ade nosine the extraction in the infused kidney decreased to 12 +/- 3% (P < 0.01 compared with the control kidney, 23 +/- 3%). 4. The total excr etion of Na+ was unchanged, but there was a minor decrease in K+ clear ance. Thus, the K+/Na+ excretion ratio decreased from a basal value of 13 +/- 2 to 10 +/- 2 (P < 0.01) at the highest dose of adenosine. The calculated renal uptake of oxygen was unchanged in the control kidney , but decreased in the adenosine-infused kidney from a basal value of 5.4 +/- 0.5 ml/min to 3.8 +/- 0.4 ml/min at the highest dose of adenos ine (P < 0.01). 5. During continued intra-arterial adenosine infusion, nitroprusside was infused (0.3-2.5 mu g min(-1) kg(-1)) for 15 min to decrease blood pressure and stimulate renin production. Mean blood pr essure decreased from 90 +/- 2 to 63 +/- 2 mmHg, whereas heart rate re mained unaffected. There were increases in the arterial concentrations of adrenaline (0.3 +/- 0.1 to 1.3 +/- 0.3 nmol/l; P < 0.01), aldoster one (136 +/- 24 to 491 +/- 144 pmol/l; P < 0.001) and renin activity ( 0.8 +/- 0.2 to 1.8 +/- 0.5 pmol) of angiotensin I h(-1) min(-1); P < 0 .05; values correspond to the basal state and 15 min of nitroprusside infusion, respectively). In the control kidney the arteriovenous conce ntration difference for renin activity increased from the basal state by 2.3 +/- 0.8 pmol of angiotensin I h(-1) ml(-1), but remained unchan ged in the adenosine-infused kidney (0.0 +/- 0.3 pmol of angiotensin I h(-1) ml(-1), P < 0.02). 6. In conclusion, the direct renal effects o f adenosine in healthy awake subjects include a local dilatation of po stglomerular vessels, thereby decreasing glomerular filtration, and a reduction in renal oxygen consumption. Furthermore, adenosine prevents an increase in renin release during nitroprusside-induced hypotension .