Regular physical exercise improves walking performance in patients affected with peripheral obliterative arterial disease (POAD). The mechanisms underlying the phenomenon are still controversial. In order to verify the hypothesis that physical conditioning of lower limbs on a treadmill and ischemic preconditioning of the heart could share some biological aspects, 14 POAD subjects underwent a training program on the treadmill consisting of five repeated submaximal exercises at five-minute and two-hour intervals preceding the maximal tolerance test. Moreover, a protocol with two daily submaximal walking exercises over one week was also performed. Pain-free and total walking distance were measured before and after they performed the program. Moreover, plasma levels of adenosine and adenosine triphosphate (ATP) were measured and polymorphonuclear (PMN) leukocyte activity was studied together with rheologic parameters. Pain-free distance was prolonged by 15.4% and 14.3%, and total distance was prolonged by 23.1% and 26.9%, in the exercises with five-minute and two-hour intervals, respectively. After one week of daily exercises, the onset of pain and the end of the test were delayed by 24% and 43.7%, respectively. An improvement in blood rheology and a reduced PMN reactivity were also observed with the three protocols, associated with an increase in plasma levels of adenosine and ATP. Similarly to ischemic preconditioning in the heart, the possibility is suggested that an adenosine-mediated mechanism may contribute to the development of physical conditioning in treadmill-trained POAD patients.

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 < 0.01), diastolic (-16%, from 80.0 +/- 7.9 to 67.2 +/- 7.0 mmHg; F = 18.97, P < 0.01) 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 < 0.01). 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.(ABSTRACT TRUNCATED AT 250 WORDS)