We investigated the effects of the adenosine antagonist caffeine on the hemodynamic response to dipyridamole infusion (0.4 mg/kg for 4 minutes). According to a randomized, placebo-controlled double-blind protocol, eight normotensive volunteers each participated in five tests: placebo after placebo, dipyridamole after placebo, and dipyridamole after 1, 2, and 4 mg/kg caffeine. Infusion of caffeine alone (4 mg/kg) induced an increase in mean arterial pressure of 6.1 +/- 0.5 mm Hg versus 1.5 +/- 0.9 mm Hg after placebo (p less than 0.05). Infusion of dipyridamole alone exerted a characteristic hemodynamic response with an increase in systolic blood pressure (+8.4 +/- 2.4 mm Hg), pulse pressure (+7.0 +/- 2.4 mm Hg), heart rate (+25.7 +/- 3.8 beats/min) and calculated rate-pressure product (+3419 mm Hg x beats per minute), all being significantly different from the changes induced by placebo. Caffeine induced a dose-dependent attenuation of the response to dipyridamole, with a significant negative correlation between the dose of caffeine on the one hand (0, 1, 2, and 4 mg/kg) and the dipyridamole-induced increments in systolic blood pressure (r = -0.53), pulse pressure (r = -0.50), heart rate (r = -0.95), and rate-pressure product (r = -0.93) on the other hand. We conclude that caffeine attenuates the hemodynamic response to dipyridamole infusion in humans in a dose-dependent fashion. Because of the wide-spread use of caffeine, this pharmacologic interaction may be of clinical importance, for example, in the diagnostic use of dipyridamole in thallium-201 myocardial imaging.
"Dipyridamole and PORH P Meijer et al Carlsson et al. (1987) previously observed an increased PORH after intravenous infusion of dipyridamole that was inhibited by intravenous theophylline. Although the conclusions of the authors fit well with our observations, this study of Carlsson et al. is difficult to interpret, as both drugs have important effects on blood pressure and heart rate when infused intravenously (Smits et al., 1991b). Unfortunately , they did not report any recordings of blood pressure or heart rate in this study. "
[Show abstract][Hide abstract] ABSTRACT: Dipyridamole enhances post-occlusive reactive hyperaemia (PORH) in the human forearm vascular bed. We hypothesize that this effect is completely mediated by increased adenosine receptor stimulation. To test this hypothesis, the effect of caffeine (an adenosine receptor antagonist) on dipyridamole-induced augmentation of PORH was explored.
The forearm vasodilator responses to three increasing periods of forearm ischaemia (2, 5 and 13 min) were determined during placebo infusion. Forty minutes after the last reperfusion period, this procedure was repeated during intra-arterial infusion of dipyridamole (7.4 nmol min(-1) per 100 ml forearm). At least 2 weeks later, this whole procedure was repeated, but now in the presence of caffeine (90 microg min(-1) per 100 ml volume).
After 2, 5 and 13 min of ischaemia, the average forearm blood flow increased to 5.6+/-0.7, 9.7+/-1.3 and 34.5+/-2.1 ml min(-1) per 100 ml. After infusion of dipyridamole into the brachial artery, these numbers were significantly increased to 7.7+/-0.8, 12.5+/-1.5 and 41.6+/-3.1 ml min(-1) per 100 ml. This response was abolished by the concomitant infusion of caffeine (6.6+/-0.5, 10.2+/-0.6, 35.1+/-2.2 (caffeine) versus 7.4+/-0.4, 10.5+/-0.6, 33.7+/-2.2 ml min(-1)per 100 ml (caffeine/dipyridamole)).
Caffeine prevented the augmenting effect of dipyridamole on PORH. This indicates that dipyridamole-induced augmentation of PORH is mediated via increased adenosine receptor stimulation as a result of elevated extracellular formation of adenosine during ischaemia.
British Journal of Pharmacology 04/2008; 153(6):1169-76. DOI:10.1038/bjp.2008.10 · 4.84 Impact Factor
"line values throughout the last 90 min of the clamp period . Both caffeine treatments ( CAF and CAF + ADR ) resulted in higher DBP compared to ADR ( Fig . 6 ) . This elevation in DBP occurred despite different adrenaline concentrations ( 0 . 62 versus 0 . 93 nm ) . These findings suggest an independent action of caffeine and confirm the results of Smits et al . ( 1991 ) who report that the haemodynamic effects of caffeine are via an adrenaline - independent mechanism ( Smits et al . 1983 ) , specifically via the inhibition of adenosine - induced vasodilation ( Smits et al . 1990 ) . Although in the present study ' s acute situation caffeine elicits an impairment in insulin - mediated whole body gluco"
[Show abstract][Hide abstract] ABSTRACT: Caffeine (CAF) impedes insulin-mediated glucose disposal (IMGD) and increases plasma adrenaline concentrations ([ADR]; 0.6 nm). While the antagonism of ADR abolishes the CAF effect, infusion of ADR (0.75 nm) has no effect on IMGD. We have now examined CAF and ADR in concert to determine whether or not they elicit an additive response on IMGD. We hypothesized that CAF + ADR would elicit a greater effect than either CAF or ADR alone (i.e. that CAF effects would not be solely attributed to ADR). Subjects (n = 8) completed four trials in a randomized manner. An isoglycaemic-hyperinsulinaemic clamp was performed 30 min after the following treatments were administered: (1) placebo capsules and saline infusion ([ADR] = 0.29 nm) (PL trial), (2) CAF capsules (dose = 5 mg kg(-1)) and saline infusion ([ADR] = 0.62 nm) (CAF trial), (3) PL capsules and ADR infusion ([ADR] = 1.19 nm) (ADR trial), and (4) CAF capsules (dose = 5 mg kg(-1)) and ADR infusion ([ADR] = 0.93 nm) (CAF + ADR trial). As expected, CAF, ADR and CAF + ADR decreased (P <or= 0.05) IMGD compared to PL. CAF + ADR resulted in a more pronounced decrease in IMGD versus PL (42%) compared to CAF (26%) or ADR (24%) alone; however, the effect was not fully additive (P = 0.08). Furthermore, CAF decreased IMGD to a similar magnitude as ADR despite a 50% lower [ADR]. In summary, while ADR contributes to the CAF-induced impairment in IMGD, it is not solely responsible for caffeine's effects.
The Journal of Physiology 09/2007; 583(Pt 3):1069-77. DOI:10.1113/jphysiol.2007.130526 · 5.04 Impact Factor
") and although levels did not significantly increase until 20 min following ingestion it is likely that the portal vein concentrations were much higher because caffeine to a large extent is extracted by the liver (Pencek et al. 2004). In addition, caffeine at concentrations of 3–9 µm, which we achieved by 15 min post-ingestion, are known to be biologically active (Smits et al. 1991). The absence of an accompanying increase in adrenaline concentrations cannot explain the lack of caffeine effect on EGP, as the higher adrenaline concentrations obtained in the HAdr trial also did not increase EGP. "
[Show abstract][Hide abstract] ABSTRACT: While caffeine impedes insulin-mediated glucose disposal in humans, its effect on endo-genous glucose production (EGP) remains unknown. In addition, the mechanism involved in these effects is unclear, but may be due to the accompanying increase in adrenaline concentration. We studied the effect of caffeine on EGP and glucose infusion rates (GIR), and whether or not adrenaline can account for all of caffeine's effects. Subjects completed three isoglycaemic-hyperinsulinaemic clamps (with 3-[(3)H]glucose infusion) 30 min after ingesting: (1) placebo capsules (n= 12); (2) caffeine capsules (5 mg kg(-1)) (n= 12); and either (3) placebo plus a high-dose adrenaline infusion (HAdr; adrenaline concentration, 1.2 nM; n= 8) or (4) placebo plus a low-dose adrenaline infusion (LAdr; adrenaline concentration, 0.75 nM; n= 6). With caffeine, adrenaline increased to 0.6 nM but no effect on EGP was observed. While caffeine and HAdr decreased GIR by 13 (P < 0.05) and 34% (P < 0.05) versus the placebo, respectively, LAdr did not result in a significant reduction (5%) in GIR versus the placebo. Due to the fact that both caffeine and LAdr resulted in similar adrenaline concentrations, but resulted in different decreases in GIR, it is concluded that adrenaline alone does not account for the effects of caffeine and additional mechanisms must be involved.
The Journal of Physiology 12/2005; 569(Pt 1):347-55. DOI:10.1113/jphysiol.2005.097444 · 5.04 Impact Factor
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