Appearance of adenosine in venous blood from the contracting gracilis muscle and its role in vasodilatation in the dog.

Abstract

SUMMARY1. In dogs anaesthetized with sodium pentobarbitone and artificially ventilated, the gracilis muscles were vascularly isolated and perfused at a constant flow rate of 51-2+9-8 ml min-1 100 g-1 muscle tissue (183+ 17-8% of resting blood flow; mean+S.E.; n = 13).2. Electrical stimulation of the cut peripheral end of the obturator nerve (6 V, 4 Hz) resulted in muscle contraction (658+118 g 100 g-1 force after 5 min), and an immediate decrease in arterial perfusion pressure from 179+15-7 mmHg to 87+10-0 mmHg (514+4-5 % decrease in vascular resistance after 2 min of contraction). Venous oxygen tension decreased from 692 + 51 mmHg to 18-5 + 1-4 mmHg (n = 6). These values did not significantly alter during the remaining period of stimulation (10-20 min).3. The concentration of adenosine in arterial plasma did not change significantly during muscle contraction (137 + 23 nM; n = 10). However, the adenosine concentrations in venous plasma showed a significant (P < 0-01) increase from a control value of 164 + 55 nM to 455+77 nM (n = 9) after 5 min of muscle contraction and remained high during the rest of the 20 min contraction. In six of the dogs adenosine concentrations were determined after 1 and 3 min of contraction and showed a smaller but statistically significant (P < 0 05) rise in venous concentration.4. During infusion of adenosine into the artery to give plasma concentrations between 0-3 /LM and 1 mm, 72-6 + 2-1 % (n = 29) of the infused adenosine was taken up by the tissues before it reached the vein. Comparison of vasodilatation and venous adenosine concentrations during adenosine infusion and muscle contractions showed that the released adenosine could contribute about 15 % to the total vasodilatation after 1 min and about 40 % between 5 and 20 min of contractions. Released adenosine could contribute about 80% to the vasodilatation that remained 5 min after the withdrawal of stimulation. Arterial perfusion pressure took 22 min to return to control, whereas adenosine release had fallen to zero within 10 min.5. These data suggest that the released adenosine could contribute to exercise hyperaemia, but is unlikely to be the main factor, particularly in the initial stage.

Adenosine Contributes to Blood Flow Regulation in the Exercising Human Leg by Increasing Prostaglandin and Nitric Oxide Formation

“…The similar arterial and venous adenosine concentrations suggest that adenosine is not released from the interstitium of exercising muscle. This observation is in contrast to observations in the isolated dog limb 22 but in agreement with the observation that the endothelium is an effective barrier for adenosine. 23 Furthermore, plasma ATP increases during exercise, 31 but adenosine does not play a role in ATP-induced vasodilation, 25,29 and the breakdown products of ATP are, therefore, likely to be rapidly taken up by erythrocytes.…”

“…In vitro evidence from studies on laboratory animals suggests that adenosine is increased in the venous efflux of contracting muscle, 21,22 as well as during hypoxia and ischemia. 23 However, because of rapid uptake by red blood cells, as well as degradation in plasma, the half-life of adenosine is estimated to be Ͻ1 second.…”

The influence of lactic acid on adenosine release from skeletal muscle in anaesthetized dogs.

“…Thus the increased adenosine release at low blood flow was likely to be caused by some other factor related to the flow restriction, rather than the oxygen lack. Both the adenosine release and the venous pH returned to control values over a time couise of about 10 min during the recovery from muscle contractions, whereas the venous oxygen tension had returned to control within the first minute after stimulation was stopped (Ballard et al 1987), indicating a possible involvement of acidity in the adenosine release.…”

“…The adenosine content of venous blood and muscle has long been known to increase during flow-restricted contractions (Berne,Rubio,Dobson & MS 8529 Curnish, 1971; Bockman, Berne & Rubio, 1976;Belloni, Phair & Sparks, 1979), whilst recent technological advances have allowed detection of the more moderate increases in venous adenosine which accompany contractions during high constant flow perfusion (Ballard, Cotterrell & Karim, 1987) or free flow perfusion (Fuchs, Gorman & Sparks, 1981;Karim, Ballard & Cotterrell, 1988). The released adenosine has been shown to make an important contribution to the steady-state vasodilatation accompanying contractions (Kille & Klabunde, 1984;Ballard et al 1987;Goonewardene & Karim, 1989), but little is known about the mechanism of the adenosine release.…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…In addition, adenosine acts on presynaptic receptors to inhibit sympathetic nerve-mediated vasoconstriction (Fuglsang and Crone, 1987). However, in studies of canine gracilis muscle, it was concluded that, although released adenosine could contribute to exercise hyperemia, it is likely not to be the main factor, particularly in the initial stage (Ballard et al, 1987;Koch et al, 1990). Adenosine, acting via A 2A receptors, contributes up to 30% of the functional hyperemic response in the hindlimb of anesthetized cats (Poucher, 1996).…”