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 awake subjects have been examined. 2. Renal blood flow and glomerular filtration rate were measured as the clearances of p-aminohippurate and inulin, respectively. After basal samplings, adenosine was infused intra-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 activation (unchanged blood pressure and catecholamine levels) during the infusion. Clearance of p-aminohippurate tended to increase, but not significantly, during adenosine infusion (518 +/- 48 ml/min basal, 563 +/- 52 ml/min during the highest dose of adenosine). The arterial plasma concentration of p-aminohippurate decreased by 9 +/- 3% (P < 0.05), consistent with a small increase in renal blood flow in the infused kidney. Inulin clearance was reduced from 115 +/- 3 to 97 +/- 2 ml/min (P < 0.001). The extraction of inulin, reflecting the filtration fraction, was 18% in both kidneys in the basal state. During infusion of adenosine the extraction in the infused kidney decreased to 12 +/- 3% (P < 0.01 compared with the control kidney, 23 +/- 3%). 4. The total excretion of Na+ was unchanged, but there was a minor decrease in K+ clearance. 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 adenosine (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 pressure decreased from 90 +/- 2 to 63 +/- 2 mmHg, whereas heart rate remained unaffected. There were increases in the arterial concentrations of adrenaline (0.3 +/- 0.1 to 1.3 +/- 0.3 nmol/l; P < 0.01), aldosterone (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 concentration difference for renin activity increased from the basal state by 2.3 +/- 0.8 pmol of angiotensin I h(-1) ml(-1), but remained unchanged 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 of adenosine in healthy awake subjects include a local dilatation of postglomerular vessels, thereby decreasing glomerular filtration, and a reduction in renal oxygen consumption. Furthermore, adenosine prevents an increase in renin release during nitroprusside-induced hypotension.