Evidence of an adenosine-dependent mechanism in the hypotensive effect of L-arginine in man

1. The hypothesis that endogenous adenosine could play a role in the haemodynamic response to l‐arginine is investigated. 2. The study has been divided into two parts. The first part was a single blind, randomized, placebo‐controlled study in which L‐arginine i.v. infusion (0.07 mmol/kg per min) in five healthy volunteers caused a significant fall in systolic (‐14.2%, from 129.0 ± 8.2 to 110.6 ± 8.5 mmHg; F= 62.89, P<0.0l), diastolic (‐16%, from 80.0 ± 7.9 to 67.2 ± 7.0 mmHg; F= 18.97, P < 0.0l) and mean (‐15.5%, from 96.4 ± 6.7 to 81.4 ± 6.5 mmHg; F= 28.78, P< 0.01) arterial blood pressure, with a concomitant increase of plasma adenosine concentration (from 244.0 ± 32.2 to 637.0 ± 43.4 nmol/L; F= 79.3 P<10.01). Maximal effects were obtained at the end of L‐arginine infusion: haemodynamic parameters returned to basal values in about 30 min while adenosine concentrations normalized in about 15 min. Saline infusion had no effect on these parameters. 3. In the second study the effect of L‐arginine i.v. infusion on arterial blood pressure, lower limb blood flow and plasma adenosine, before and after theophylline treatment (1000 mg/day for 3 days, p.o.) was examined. In 10 healthy volunteers the i.v. infusion of l‐arginine (0.07 mmol/kg per min) was followed by the same haemodynamic changes as reported above and by a Significant increase in lower limb blood flow (+ 36.7%, from 2.18 ± 0.40 to 2.98 ± 0.71mL/min/lOOmL;t = 4.61, P< 0.01). Pretreatment with theophylline, an adenosine‐receptor antagonist, did not affect basal values of arterial pressure, lower limb blood flow and adenosine concentration. The pretreatment with theophylline reduced maximal decrease in systolic pressure (‐ 8.2 vs ‐15%), in mean pressure (‐ 9.9 vs ‐13.7%) and maximal increase in lower limb blood flow (+19 vs + 37%) caused by i.v. infusion of l‐arginine (0.07 mmol/kg per rnin). Such a treatment allowed a progressive restoration of basal blood pressure values and of blood flow, during the second half of l‐arginine infusion. This observation was confirmed by the analysis of the area under the curves (AUC). A significant difference in AUC values before and after treatment was obtained for systolic pressure (t = 8.25, P< O.Ol), mean pressure (t= 6.67, P<0.0l) and blood flow (t= 2.31, P[removed]