Theophylline inhibits isoproterenol-induced coronary dilatation in the isolated perfused rat heart

Tanaka, Toshiko; Fukumoto, Tazuru; Ochi, Toya; Kuroiwa, Akio

doi:10.1016/0167-5273(90)90128-r

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…However, theophylline is also known to block adenosine receptors in human skin as adenosine-induced cutaneous vasodilatation is largely diminished by theophylline (Fujii et al 2015). Isoproterenol may induce vasodilatation through increases in adenosine (Tanaka et al 1990), and adenosine may activate NOS (Nyberg et al 2010). We also demonstrated for the first time that adenosine-induced cutaneous vasodilatation is partly a result of NOS-dependent mechanisms (Fig.…”

Section: Adenosine Mechanismsmentioning

confidence: 53%

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Nitric oxide synthase and cyclooxygenase modulate β‐adrenergic cutaneous vasodilatation and sweating in young men

Fujii

McNeely

Kenny

2016

The Journal of Physiology

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Key pointsr β-Adrenergic receptor agonists such as isoproterenol induce cutaneous vasodilatation and sweating in humans, but the mechanisms underpinning this response remain unresolved.r Using intradermal microdialysis, we evaluated the roles of nitric oxide synthase (NOS) and cyclooxygenase (COX) in β-adrenergic cutaneous vasodilatation and sweating elicited by administration of isoproterenol.r We show that while NOS contributes to β-adrenergic cutaneous vasodilatation, COX restricts cutaneous vasodilatation.r We also show that combined inhibition of NOS and COX augments β-adrenergic sweating r These new findings advance our basic knowledge regarding the physiological control of cutaneous blood flow and sweating, and provide important and new information to better understand the physiological significance of β-adrenergic receptors in the skin.Abstract β-Adrenergic receptor agonists such as isoproterenol can induce cutaneous vasodilatation and sweating in humans, but the mechanisms underpinning this response remain unresolved. We evaluated the hypotheses that (1) nitric oxide synthase (NOS) contributes to β-adrenergic cutaneous vasodilatation, whereas cyclooxygenase (COX) limits the vasodilatation, and (2) COX contributes to β-adrenergic sweating. In 10 young males (25 ± 5 years), cutaneous vascular conductance (CVC) and sweat rate were evaluated at four intradermal forearm skin sites infused with (1) lactated Ringer solution (control), (2) 10 mM N ω -nitro-L-arginine (L-NNA), a non-specific NOS inhibitor, (3) 10 mM ketorolac, a non-specific COX inhibitor, or (4) a combination of L-NNA and ketorolac. All sites were co-administered with a high dose of isoproterenol (100 μM) for 3 min to maximally induce β-adrenergic sweating (β-adrenergic sweating is significantly blunted by subsequent activations). Approximately 60 min after the washout period, three incremental doses of isoproterenol were co-administered (1, 10 and 100 μM each for 25 min). Increases in CVC induced by the first and second 100 μM isoproterenol were attenuated by L-NNA alone, and those in response to all doses of isoproterenol were reduced by L-NNA with co-infusion of ketorolac (all P ࣘ 0.05). Ketorolac alone augmented increases in CVC induced by 10 μM and by the second 100 μM isoproterenol (both P ࣘ 0.05). While isoproterenol-induced sweating was not affected by the separate administration of L-NNA or ketorolac (all P > 0.05), their combined administration augmented sweating elicited by the first 3 min of 100 μM isoproterenol (P = 0.05). We show that while NOS contributes to β-adrenergic cutaneous vasodilatation, COX restrains the vasodilatation. Finally, combined inhibition of NOS and COX augments β-adrenergic sweating.

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Section: Adenosine Mechanismsmentioning

confidence: 53%

“…Isoproterenol may induce vasodilatation through increases in adenosine (Tanaka et al . ), and adenosine may activate NOS (Nyberg et al . ).…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide synthase and cyclooxygenase modulate β‐adrenergic cutaneous vasodilatation and sweating in young men

Fujii

McNeely

Kenny

2016

The Journal of Physiology

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Theophylline increases coronary vascular tone in humans: evidence for a role of endogenous adenosine in flow regulation

Edlund

Sollevi

1995

Acta Physiologica Scandinavica

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To elucidate the role of adenosine in coronary vasoregulation, we studied the effects of adenosine antagonism (by theophylline) on coronary blood flow at different levels of adenosine formation (stimulated by hypoxia and exercise). Six healthy subjects were studied. Coronary sinus (CS) blood flow (thermodilution) and cardiac oxygen extraction [(A-CS)O2D] were determined while breathing room air at rest, and 12% oxygen, both at rest and during light exercise, on two occasions. One of the experiments was performed during infusion of theophylline. The basal CS flow was 118 (67-168) mL min-1 (mean and 95% confidence interval), and the (A-CS)O2D was 125 (111-142) mL L-1. Inhalation of 12% O2 decreased the arterial haemoglobin oxygen saturation to 83 (80-86)% at rest and to 77 (73-81)% during exercise. CS flow increased to 167 (93-214) and 261 (179-343) mL min-1, respectively, and (A-CS)O2D decreased to 102 (85-119) and 94 (77-111) mL L-1, respectively. Theophylline, at a dose lacking effects on myocardial work, markedly attenuated the coronary flow response to exogenous adenosine, and decreased CS flow to 89 (58-119), 120 (79-161) and 190 (162-218) mL min-1 at normoxic rest, hypoxic rest and hypoxic exercise, respectively. The overall decrease amounted to 23% (P < 0.05). The calculated coronary vascular conductance also decreased by 23% (P < 0.05) and (A-CS)O2D increased by 15% (P < 0.001). In conclusion, the data support the hypothesis that endogenous adenosine is involved in regulation of human coronary tone.

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Coronary blood flow regulation in exercising swine involves parallel rather than redundant vasodilator pathways

Merkus

Haitsma

Fung

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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In dogs, only combined blockade of vasodilator pathways [via adenosine receptors, nitric oxide synthase (NOS) and ATP-sensitive K+ (KATP) channels] results in impairment of metabolic vasodilation, which suggests a redundancy design of coronary flow regulation. Conversely, in swine and humans, blocking KATP channels, adenosine receptors, or NOS each impairs coronary blood flow (CBF) at rest and during exercise. Consequently, we hypothesized that these vasodilators act in parallel rather than in redundancy to regulate CBF in swine. Swine exercised on a treadmill (0-5 km/h), during control and after blockade of KATP channels (with glibenclamide), adenosine receptors [with 8-phenyltheophylline (8-PT)], and/or NOS [with Nomega-nitro-l-arginine (l-NNA)]. l-NNA, 8-PT, and glibenclamide each reduced myocardial O2 delivery and coronary venous O2 tension. These effects of l-NNA, 8-PT, and glibenclamide were not modified by simultaneous blockade of the other vasodilators. Combined blockade of KATP channels and adenosine receptors with or without NOS inhibition was associated with increased H+ production and impaired myocardial function. However, despite an increase in O2 extraction to >90% during administration of l-NNA + 8-PT + glibenclamide, vasodilator reserve could still be recruited during exercise. Thus in awake swine, loss of KATP channels, adenosine, or NO is not compensated for by increased participation of the other two vasodilator mechanisms. These findings suggest a parallel rather than a redundancy design of CBF regulation in the porcine circulation.

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Theophylline inhibits isoproterenol-induced coronary dilatation in the isolated perfused rat heart

Cited by 4 publications

References 26 publications

Nitric oxide synthase and cyclooxygenase modulate β‐adrenergic cutaneous vasodilatation and sweating in young men

Nitric oxide synthase and cyclooxygenase modulate β‐adrenergic cutaneous vasodilatation and sweating in young men

Theophylline increases coronary vascular tone in humans: evidence for a role of endogenous adenosine in flow regulation

Coronary blood flow regulation in exercising swine involves parallel rather than redundant vasodilator pathways

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