Evidence for an Antagonism Between Caffeine and Adenosine in the Human Cardiovascular System

Smits, P.; Boekema, Paul J.; Abreu, Ronney A. De; Thien, Theo; Laar, A. van ‘t

doi:10.1097/00005344-198708000-00002

Cited by 120 publications

(82 citation statements)

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“…From a pharmacological point of view it seems of interest to develop agents with a comparable local effect on the myocardium (10). Within this concept, long-acting adenosine receptor agonists are not useful because these drugs elicit pharmacological effects, not only during ischemia but continuously, and not only in the myocardium but in nearly all organ systems, resulting in a large list of side effects (11,12). Inhibition of the cellular uptake of extracellular adenosine might be an alternative approach to circumvent the disadvantages of intravenous adenosine infusions (13).…”

Section: Introductionmentioning

confidence: 99%

Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection.

Rongen¹,

Smits²,

Donck³

et al. 1995

J. Clin. Invest.

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In 12 healthy male volunteers (27-53 yr), a placebo-controlled randomized double blind cross-over trial was performed to study the effect of the intravenous injection of 0.25, 0.5, 1, 2, 4, and 6 mg draflazine (a selective nucleoside transport inhibitor) on hemodynamic and neurohumoral parameters and ex vivo nucleoside transport inhibition. We hypothesized that an intravenous draflazine dosage without effect on hemodynamic and neurohumoral parameters would still be able to augment the forearm vasodilator response to intraarterially infused adenosine. Heart rate (electrocardiography), systolic blood pressure (Dinamap 1846 SX; Critikon, Portanje Electronica BV, Utrecht, The Netherlands) plasma norepinephrine and epinephrine increased dose-dependently and could almost totally be abolished by caffeine pretreatment indicating the involvement of adenosine receptors. Draflazine did not affect forearm blood flow (venous occlusion plethysmography). Intravenous injection of 0.5 mg draflazine did not affect any of the measured hemodynamic parameters but still induced a significant ex vivo nucleoside-transport inhibition of 31.5±4.1% (P < 0.05 vs placebo). In a subgroup of 10 subjects the brachial artery was cannulated to infuse adenosine (0.15, 0.5, 1.5, 5, 15, and 50 ,ug/100 ml forearm per min) before and after intravenous injection of 0.5 mg draflazine. Forearm blood flow amounted 1.9+0.3 ml/100 ml forearm per min for placebo and 1.8±0.2, 2.0±0.3, 3.8±0.9, 6.3±1.2, 11.3±2.2, and 19.3±3.9 ml/100 ml forearm per min for the six incremental adenosine dosages, respectively. After the intravenous draflazine infusion, these values were 1.6±0.2 ml/100 ml forearm per min for placebo and 2.1±0.3, 3.3±0.6, 5.8±1.1, 6.9±1.4, 14.4±2.9, and 23.5±4.0 ml/100 ml forearm per min, respectively (Friedman ANOVA: P < 0.05 before vs after draflazine infusion). In conclusion, a 30-50% inhibition of adenosine transport significantly augments the fore- arm vasodilator response to adenosine without significant systemic effects. These results suggest that draflazine is a feasible tool to potentiate adenosine-mediated cardioprotection in man. (J. Clin. Invest. 1995. 95:658-668.)

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Section: Introductionmentioning

confidence: 99%

Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection.

Rongen¹,

Smits²,

Donck³

et al. 1995

J. Clin. Invest.

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“…Vasorelaxation results in decreased wave reflection indices, whereas vasoconstriction has the opposite effect. As it has been demonstrated, caffeine exerts its main cardiovascular effects through the antagonism of adenosine and the release of catecholamines, both resulting in vasoconstriction (Robertson et al, 1978;Smits et al, 1987;Varani et al, 1999;Corti et al, 2002;Lane et al, 2002;Brodmann et al, 2003;Saboury et al, 2003). In this context, it has been shown that norepinephrine infusion increases augmentation index (Wilkinson et al, 2001;Stewart et al, 2003).…”

Section: Mechanismsmentioning

confidence: 99%

Effect of chronic coffee consumption on aortic stiffness and wave reflections in hypertensive patients

Alexopoulos

et al. 2006

Eur J Clin Nutr

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Objective: Aortic stiffness and wave reflections are important markers and prognosticators of cardiovascular risk. Caffeine increases acutely aortic stiffness and wave reflections. Furthermore, chronic coffee consumption is associated with increased aortic stiffness and wave reflections in normotensive subjects. In the present study, we aimed to assess the association between chronic coffee consumption, and aortic stiffness and wave reflections in hypertensive patients. Design: Epidemiological survey. Setting: Hypertension Unit, University Hospital. Subjects-methods: We examined 259 never-treated hypertensives (age 50712 years, 165 males) without diabetes mellitus, who were asked to describe in detail the type and amount of coffee they consumed. Carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) were measured non-invasively as indices of aortic stiffness and wave reflections, respectively. Results: When controlled for gender, age, height, smoking status, heart rate, mean pressure, HDL cholesterol and hsCRP, AIx was found to be higher with increasing daily coffee consumption. Post hoc analysis revealed that all groups of coffee consumption had higher AIx compared to no-consumption. PWV did not differ among groups of daily coffee consumption. Each participant had 35% higher relative risk of having high AIx for each cup (150 ml) of coffee per day, and 40% higher relative risk for each 10 cup-years. Conclusions: Coffee consumption is associated with increased wave reflections, but not aortic stiffness in never-treated hypertensive patients. This finding may have important clinical implications for cardiovascular health in hypertensive subjects. Sponsorship: None.

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“…25 Fasting serum caffeine levels reflect the clearance rate of caffeine. The greatest acute blood pressure response to caffeine occurred in those subjects with the lowest baseline caffeine levels 19 and in caffeine nonusers 6 ; a negative correlation was found between the coffee-induced blood pressure increase and the fasting plasma caffeine level in 30 normotensive healthy subjects.…”

Section: Mechanismsmentioning

confidence: 99%

Effect of decaffeinated versus regular coffee on blood pressure. A 12-week, double-blind trial.

et al. 1989

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The effect of decaffeinated versus regular coffee on blood pressure and heart rate was investigated. In a randomized double-blind, crossover trial, 45 healthy volunteers (23 women and 22 men, 25-45 years old) with a habitual intake of 4-6 cups coffee/day received 5 cups of regular coffee each day for a period of 6 weeks, and 5 cups of decaffeinated coffee for the next 6 weeks or vice versa. The background diet was kept constant. The total amount of caffeine ingested was 40 mg during the decaffeinated coffee period and 445 mg during the regular coffee period. Use of decaffeinated coffee led to a significant but small decrease in systolic (mean±SEM, -1 . 5 ± 0 . 4 mm Hg; />=0.002) and diastolic (-1.0±0.4 mm Hg; p=0.017) ambulant blood pressure and to a small increase in ambulant heart rate (+1.3±0.6 beats/min; p=0.031). Individual differences in rate of caffeine metabolism did not explain differences in long-term response of blood pressure to caffeine. We conclude that in normotensive adults replacement of regular by decaffeinated coffee leads to a real but small fall in blood pressure. However, it remains to be established whether a mass switch from regular to decaffeinated coffee would significantly reduce the total incidence of hypertension-related disorders. (Hypertension 1989;14:563-569) C offee is the most widely used stimulant in Western society. In the Netherlands, 94% of adults drink at least 1 cup/day, and the per capita intake is 4.5 cups/day.1 An increasing proportion of consumers is switching from regular to decaffeinated coffee. In the Netherlands, the market share of decaffeinated coffee grew from 2% in 1984 to 4% in 1987. In the United States, the proportion is already 20%.2 The switch is motivated partly by the well-documented negative effects of caffeine on the quality of sleep and partly by other purported negative effects, including those on the cardiovascular system. However, surprisingly little is known about the actual long-term effect of switching to decaffeinated coffee and how this switch will affect risk factors for coronary heart disease.Epidemiological surveys on the relation between coffee consumption and blood pressure have yielded Supported by Grant 87.026 from the Netherlands Heart Foundation. The coffee was a gift of the Dutch association of coffee toasters and tea packers.Received May 2, 1989; accepted in revised form June 29,1989. contradictory findings.3 -5 Controlled trials showed that in subjects who have abstained from caffeine for a number of days blood pressure rises acutely after a caffeine load. The extent of this acute pressor effect of caffeine depends on the amount and frequency of previous caffeine intake and on the rate of caffeine metabolism; subjects with a high coffee intake appear to be less sensitive to the pressure-elevating effect of caffeine.6 This was confirmed by one experiment that showed no effect of caffeine consumption on blood pressure after 4 weeks 7 ; however, the diet was not controlled, and the power of this trial was small.In the present study...

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Evidence for an Antagonism Between Caffeine and Adenosine in the Human Cardiovascular System

Cited by 120 publications

References 0 publications

Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection.

Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection.

Effect of chronic coffee consumption on aortic stiffness and wave reflections in hypertensive patients

Effect of decaffeinated versus regular coffee on blood pressure. A 12-week, double-blind trial.

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