Vascular Effects Of Adenosine Research Articles

Adenosine receptors in the response to sepsis: what do receptor-specific knockouts tell us?

in this issue Dr. Lee and colleagues (8a) demonstrate that the A3 adenosine receptor subtype (A3R) protects against a septic challenge. In this regard, the A3R joins the A1R and A2AR in similar investigations. Although the focus of their investigation was the A3R, Dr. Lee and colleagues directly

Dietary Caffeine Consumption Modulates fMRI Measures

Caffeine is the most widely used stimulant in the world. The stimulant effects of caffeine are mediated through its antagonistic properties on neuronal adenosine receptors. In addition, caffeine blocks neurovascular adenosine receptors and decreases cerebral perfusion. Although the effects of caffeine on blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging measures are extremely important, there are few studies addressing this issue in the literature. Because chronic caffeine use causes an upregulation of adenosine receptors, the differential effects of caffeine in low and high users is of particular interest. The present study was designed to test the hypothesis that caffeine has differential effects on the BOLD signal in high and low caffeine users. We demonstrated that the BOLD signal change in visual cortex was significantly greater in high users than in low users in the presence of caffeine. In addition, the magnitude of the BOLD signal was significantly correlated with caffeine consumption. We propose that the outcome observed here was due to an upregulation of adenosine receptors in high users, resulting in differential contributions of the neural and vascular effects of adenosine in the two study populations.

Dietary Caffeine Consumption Modulates fMRI Measures

Caffeine is the most widely used stimulant in the world. The stimulant effects of caffeine are mediated through its antagonistic properties on neuronal adenosine receptors. In addition, caffeine blocks neurovascular adenosine receptors and decreases cerebral perfusion. Although the effects of caffeine on blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging measures are extremely important, there are few studies addressing this issue in the literature. Because chronic caffeine use causes an upregulation of adenosine receptors, the differential effects of caffeine in low and high users is of particular interest. The present study was designed to test the hypothesis that caffeine has differential effects on the BOLD signal in high and low caffeine users. We demonstrated that the BOLD signal change in visual cortex was significantly greater in high users than in low users in the presence of caffeine. In addition, the magnitude of the BOLD signal was significantly correlated with caffeine consumption. We propose that the outcome observed here was due to an upregulation of adenosine receptors in high users, resulting in differential contributions of the neural and vascular effects of adenosine in the two study populations.

Vascular effects of adenosine and its analogues

AbstractThe main action of adenosine on vascular beds is vasodilation via A2 receptors. In addition, A1 receptors are found in some blood vessels, where they cause contraction. Traditionally, adenosine‐induced vasodilation in vitro has been attributed to A2A receptor activation; however, it is now clear that A2B receptors are also involved in the regulation of vascular tone. Endothelium dependence of A2 receptor‐mediated responses is variable; in some tissues they are blocked by removal of endothelium and/or inhibition of NO‐synthase and in some they are not. In addition to A2 receptor‐mediated relaxation, there is much evidence that relaxations to adenosine and some of its analogues can also be mediated by a mechanism which cannot be blocked by adenosine receptor antagonists. There is evidence that these responses are endothelium‐ and NO‐independent and that, under conditions where adenosine is taken up into cells, relaxations to the endogenous ligand are entirely mediated by this mechanism, suggesting it is of physiological significance. Drug Dev. Res. 52:346–349, 2001. © 2001 Wiley‐Liss, Inc.

Preserved vasodilator response to adenosine in insulin-dependent diabetes mellitus.

Experimental data derived from animal models suggest that the endogenous nucleoside adenosine has important cardioprotective properties. The potent vasodilator effects of adenosine may contribute to this cardioprotection as ischaemia-induced release of endogenous adenosine has been suggested to adjust local blood flow to the metabolic demands of the tissue. Interestingly, the vascular effects of adenosine appeared to be impaired in animal models for diabetes mellitus. This observation may be of importance with respect to the increased cardiovascular mortality in diabetes. Therefore, the authors investigated the in vivo vasodilator effects of adenosine in insulin-dependent diabetic patients. In 12 uncomplicated insulin-dependent male diabetic patients and 12 healthy male age-matched subjects, the brachial artery was cannulated for infusion of adenosine (0 center dot 15, 0 center dot 5, 5, 15 and 50 mu g 100(-1) mL min-1) and for measurement of mean arterial pressure (MAP). Forearm blood flow (FBF) was measured by venous occlusion mercury-in-silastic strain gauge plethysmography. Maximal vasodilatation was assessed by standardized post occlusive reactive hyperaemia (PORH). Baseline forearm blood flow was 2 center dot 7 +/- 0 center dot 4 and 1 center dot 8 +/- 0 center dot 2 mL 100(-1) mL min-1 for the diabetic patients and control group respectively. In the diabetic patients, adenosine infusion raised forearm blood flow to 2 center dot 4 +/- 0 center dot 4, 2 center dot 6 +/- 0 center dot 4, 4 center dot 4 +/- 0 center dot 7, 6 center dot 3 +/- 1 center dot 0, 9 center dot 8 +/- 1 center dot 5 and 14 center dot 2 +/- 2 center dot mL 100(-1) mL min-1 for the respective dosages. In the control group these values were 1 center dot 7 +/- 0 center dot 2, 1 center dot 9 +/- 0 center dot 3, 3 center dot 2 +/- 0 center dot 8, 6 center dot 0 +/- 1 center dot 2, 10 center dot 9 +/- 2 center dot 1 and 17 center dot +/- 3 center dot 4 mL 100(-1) mL min-1 respectively (P > 0 center dot 1 for between group comparison). Forearm blood flow at the contralateral side was not significantly affected by the placebo and adenosine infusions. Similar results were obtained when results were expressed as changes in forearm vascular resistance or forearm blood flow ration (FBF infused arm/FBF control arm). Maximal vasodilatation did not differ between the two groups. The authors conclude that the forearm vasodilator response to adenosine is preserved in uncomplicated insulin-dependent diabetic patients. This observation argues against a primary role of a reduced adenosine responsiveness in the cardiovascular sequelae of diabetes.

Implications of the Coronary Vascular Endothelium as Mediator of the Vasodilatory and Dromotropic Actions of Adenosine

Recent studies have shown that the vasodilatory response of adenosine is partially endothelium dependent. Therefore, to further characterize the physiologic role of the vascular endothelium as mediator of adenosine's cardiovascular effects, we have examined in isolated perfused guinea-pig hearts the dromotropic and vascular effects of adenosine in the presence of the adenosine antagonist, XAC, covalently conjugated to latex microspheres of 0.07 μm diameter. Our results demonstrate that intravascular infusion of the microsphere XAC conjugates abolishes the vasodilatory and negative dromotropic effects of infused adenosine, and inhibits the dromotropic effects of hypoxia. As these particles because of their size remain intravascularly confined, we conclude that the dromotropic and vasodilatory effects of exogenous adenosine, and the dromotropic effects of hypoxia (endogenous adenosine), arise from the intravascular adenosine compartment acting by way of the vascular endothelium. In addition, while neither the temporal course of vasodilation nor the steady state of vasodilation cause by hypoxia were influenced by unconjugated XAC, our results do show that the microsphere XAC conjugate increase the time necessary for maximum vasodilation to occur during hypoxia.