Aminophylline and interstitial adenosine during sustained exercise hyperemia

Thompson, Loren P.; Gorman, Mark W.; Sparks, Harvey V.

doi:10.1152/ajpheart.1986.251.6.h1232

Cited by 16 publications

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“…However, the same group determined that adenosine could contribute to around 40% of the hyperaemia observed in the later stages of exercise (Ballard et al 1987). The use of the adenosine receptor antagonist theophylline (aminophylline) has also produced equivocal results (Mohrman & Heller, 1984;Proctor, 1984;Thompson, Gorman & Sparks, 1986). Theophylline, although possessing adenosine receptor antagonist properties (pA2 = 5, Collis & Pettinger, 1982), is not an ideal compound to use since it is also able to inhibit cyclic AMP phosphodiesterase activity (Persson, Erjefalt & Karlsson, 1981).…”

Section: Discussionmentioning

confidence: 99%

The role of adenosine in exercise hyperaemia of the gracilis muscle in anaesthetized cats.

Poucher¹,

Nowell²,

Collis³

1990

The Journal of Physiology

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SUMMARY1. A number of metabolites have been proposed to control the vascular tone of skeletal muscle during exercise. The present study was designed to investigate the role of adenosine in this response by determining the effect of the adenosine receptor antagonist 8-phenyltheophylline.2. The gracilis muscle of anaesthetized cats was exposed and made to contract by stimulating the obturator nerve (at 1 Hz, 5 V, 041 ms) for 20 min. Gracilis muscle blood flow and tension were measured during exercise and for 20 min following exercise. Initially this was performed in each animal during the infusion of a vehicle solution (50% polyethylene glycol 400, 50% 0'1 M-NaOH, 01 ml min' i.v.). Exercise was then repeated during infusion of either further vehicle (group I), 8-phenyltheophylline (group II) or 3-propylxanthine (group III), both at 2-7 x 107 mol min' kg-.3. In group 1 (n = 4) gracilis muscle blood flow during the first exercise period increased by 47-5 + 11-3 ml min-' (110 g)-' and gracilis muscle tension by 8-6 + 1X3 kg (100 g muscle mass)-1 at 20 min of exercise. These responses were not significantly different when repeated. 4. In group II (n = 5), blood flow increased by 46-9 + 9.9 ml min' (100 g)-1 and tension by 6-5 + 0-7 kg (100 g muscle mass)-1 during vehicle infusion. Infusion of 8-phenyltheophylline at a rate which abolished the vasodilatation response to 2-chloroadenosine, significantly reduced the muscle blood flow increase to 19-8 + 2-7 ml min' (100 g muscle mass)-1 (P < 0-05) but the tension response was unaffected (increased by 7-0+0-8 kg (100 g muscle mass)-'). 8-Phenyltheophylline did not affect gracilis muscle blood flow or tension at rest.5. Administration of 3-propylxanthine, which did not modify the vasodilatation response to 2-chloroadenosine, failed to alter the vascular responses to muscle contraction.6. These results suggest that activation of adenosine receptors can contribute to up to 40 % of the vasodilatation observed during isometric twitch contraction of the gracilis muscle of cats.

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Section: Discussionmentioning

confidence: 99%

The role of adenosine in exercise hyperaemia of the gracilis muscle in anaesthetized cats.

Poucher¹,

Nowell²,

Collis³

1990

The Journal of Physiology

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“…Several studies have shown that adenosine is indeed a powerful vasodilator substance (Haddy et al 1967;Granger et al 1978;Berne et al 1983;Lautt and Legare 1985;Eintrei and Calsson 1986;Dobson et al 1986;Thompson et al 1986). Acetate is known to be metabolized into acetyl CoA with the generation of adenosine monophssphate (5'-AMP) from ATP (Liang and Lowenstein 1978;Puig and Fox 1984).…”

Section: Introductionmentioning

confidence: 99%

New insights on the mechanism of the alcohol-induced increase in portal blood flow

Orrego¹,

Carmichael²,

Israel³

1988

Can. J. Physiol. Pharmacol.

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Acute administration of ethanol increases portal blood flow by 40-60%. This increase in blood flow compensates for the increase in O2 consumption that follows alcohol intake and may play a protective role against hypoxic hepatocellular necrosis. We have investigated the mechanism of this hemodynamic effect of ethanol in the rat using the labeled microsphere technique. We ruled out a direct role of systemic glucagon and of acetaldehyde in mediating the increase in portal flow. However, the increase in flow is maximal at a blood ethanol concentration of 3.5 mM, corresponding to that required to achieve the Vmax of alcohol dehydrogenase, and is suppressed by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Alcohol ingestion results in zonal liver hypoxia and in increases in acetate, both of which have been shown to increase the levels of adenosine, a potent vasodilator, in blood and tissues. Ethanol produces a 400% increase in arterial adenosine. Adenosine infusion leads to a dose-dependent increase in portal blood flow of up to 100%, an effect that is suppressed by administration of 8-phenyltheophylline, an antagonist of adenosine at A1 and A2 receptors. Similarly, the ethanol-induced increase in portal blood flow is fully suppressed by 8-phenyltheophylline. In conclusion, adenosine appears to play an important role in the mechanism by which ethanol increases portal blood flow.

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“…Several of these investigators suggested that their inability to identify an important role for adenosine may be attributed to inadequate blockade of endogenously released adenosine, despite demonstration of effective blockade to exogenously administered adenosine (Honig & Frierson, 1980;Mohrman & Heller, 1984;Thompson et al 1986). Whatever the source of endogenous adenosine (skeletal muscle, neuronally released purines, other), the possible sites of adenosine's action include a direct vasodilatory effect on vascular smooth muscle mediated by the A2 subtype of the Pl-purinergic receptor, and inhibition of noradrenaline release from sympathetic nerve terminals by binding to presynaptic A1-purinergic receptors (Verhaege, Vanhoutte & Shepherd, 1977;Bruns, Lu & Pugsley, 1987).…”

Section: Discussionmentioning

confidence: 99%

“…Most of the studies during free-flow exercise have failed to identify a role for adenosine in the hyperaemic response (Phair & Sparks, 1979;Hester, Guyton & Barber, 1982;Mohrman & Heller, 1984; Klabunde, 1986; Thompson, Gorman & Sparks, 1986; Klabunde, Laughlin, & Armstrong, 1988), but the results of two studies support the hypothesis that adenosine is at least partially involved in the hyperaemia associated with skeletal muscle activity (Proctor & Duling, 1982; Steffen, McKenzie, Bockman & Haddy, 1983). Fuchs, Gorman & Sparks (1986) demonstrated that there was an increased release of adenosine into the venous plasma during free-flow exercise in isolated, perfused dog calf muscles, but they did not find a correlation between adenosine release and exercise blood flow.…”

Section: Introductionmentioning

confidence: 99%

Adenosine is not essential for exercise hyperaemia in the hindlimb in conscious dogs.

Koch

Britton

Metting

1990

The Journal of Physiology

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SUMMARY1. The contribution of endogenous adenosine to the increase in hindlimb blood flow that occurs during treadmill exercise was evaluated in conscious dogs. We postulated that if adenosine is essential for the hindlimb hyperaemic response, then pharmacological treatment of the animals with adenosine receptor antagonists should decrease hindlimb blood flow during treadmill exercise.2. A total of twenty-three dogs were chronically instrumented for measurement of aortic blood pressure and hindlimb blood flow using electromagnetic or Doppler flow probes on the left external iliac artery. Measurements of arterial blood pressure, hindlimb blood flow and heart rate were made during steady-state treadmill exercise in both the presence and the absence of adenosine receptor antagonists. Four different protocols were performed using different routes of administration of two adenosine receptor antagonists. Aminophylline was used in most of the experiments, and the effects of the more potent antagonist, 8-phenyltheophylline, were also evaluated. In addition, the dogs exercised at varying intensities ranging from a low level of 5 5 km h-1 at 0 % gradient to a high intensity of 5-5 km h-' at 21 % gradient.3. Aminophylline given as a single intravenous dose, or as a constant infusion either intravenously or directly into the hindlimb artery, did not decrease hindlimb blood flow at low, moderate or high intensities of exercise. Likewise, the blockade of adenosine receptors with 8-phenyltheophylline, given systemically or as a bolus injection administered directly into the hindlimb circulation during moderate exercise, did not attenuate the hindlimb blood flow response.4. Our data demonstrate that exercise hyperaemia of the hindlimb is not reduced by antagonism of adenosine receptors. These findings are consistent with the hypothesis that adenosine is not an essential mediator of hindlimb vasodilatation during exercise.

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Aminophylline and interstitial adenosine during sustained exercise hyperemia

Cited by 16 publications

References 0 publications

The role of adenosine in exercise hyperaemia of the gracilis muscle in anaesthetized cats.

The role of adenosine in exercise hyperaemia of the gracilis muscle in anaesthetized cats.

New insights on the mechanism of the alcohol-induced increase in portal blood flow

Adenosine is not essential for exercise hyperaemia in the hindlimb in conscious dogs.

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