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In normal hearts, myocardial perfusion is fairly well matched to regional metabolic demand, although both are distributed heterogeneously. Nonuniform regional metabolic vulnerability during coronary stenosis would help to explain nonuniform necrosis during myocardial infarction. In the present study, we investigated whether metabolismperfusion correlation diminishes during coronary stenosis, indicating increasing mismatch of regional oxygen supply to demand. Thirty anesthetized male pigs were studied: controls without coronary stenosis (n = 11); group I, left anterior descending (LAD) coronary stenosis leading to coronary perfusion pressure reduction to 70 mmHg (n = 6); group II, stenosis with perfusion pressure of about 35 mmHg (n = 6); and group III, stenosis with perfusion pressure of 45 mmHg combined with adenosine infusion (n = 7). [2-13C]- and [1,2-13C]acetate infusion was used to calculate regional O2 consumption from glutamate NMR spectra measured for multiple tissue samples of about 100 mg dry mass in the LAD region. Blood flow was measured with microspheres in the same regions. In control hearts without stenosis, regional oxygen extraction did not correlate with basal blood flow. Average myocardial O2 delivery and consumption decreased during coronary stenosis, but vasodilation with adenosine counteracted this. Regional oxygen extraction was on average decreased during stenosis, suggesting adaptation of metabolism to lower oxygen supply after half an hour of ischemia. Whereas regional O2 delivery correlated with O2 consumption in controls, this relation was progressively lost with graded coronary hypotension but partially reestablished by adenosine infusion. Therefore, coronary stenosis leads to heterogeneous metabolic stress indicated by decreasing regional O2 supply to demand matching in myocardium during partial coronary obstruction. [ABSTRACT FROM AUTHOR]

Our previous study showed that stimulation of adenosine A1 receptors located in the nucleus of the solitary tract (NTS) exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and 3-adrenergic vasodilation versus vasoconstriction mediated by neural and unknown humoral factors. In the present study we investigated the relative contribution of three major potential humoral vasoconstrictors: vasopressin, angiotensin II, and norepinephrine in this response. In urethane-chioralose anesthetized rats we compared the integral changes in iliac vascular conductance evoked by microinjections into the NTS of the selective A1 receptor agonist N6-cyclopentyladenosine (CPA; 330 pmol in 50 nI) in intact (Int) animals and following: V1 vasopressin receptor blockade (VX), angiotensin II AT1 receptor blockade (ATX), bilateral adrenalectomy + ganglionic blockade (ADX + GX; which eliminated the potential increases in circulating norepinephrine and epinephrine), ADX + OX + VX and ADX + OX + VX + ATX. In mt animals, stimulation of NTS A1 adenosine receptors evoked typical variable responses with prevailing pressor and vasoconstrictor effects. VX reversed the responses to depressor ones. ATX did not significantly alter the responses. ADX + GX accentuated pressor and vasoconstrictor responses, whereas ADX + OX + VX and ADX + OX + VX + ATX virtually abolished the responses. Stimulation of NTS A1 adenosine receptors increased circulating vasopressin over fourfold (26.4 ± 10.4 vs. 117.0 ± 19 pg/mI). These data strongly suggest that vasopressin is a major vasoconstrictor factor opposing 3-adrenergic vasodilation in iliac vascular responses triggered by stimulation of NTS A1 adenosine receptors, whereas angiotensin II and norepinephrine do not contribute significantly to the vasoconstrictor responses. [ABSTRACT FROM AUTHOR]

The adenosine A2A receptor (A2AR) enhances cardiac contractility, and the adeno- sine A1R receptor (A1R) is antiadrenergic by reducing the adrenergic ~ receptor (I3iR)-elicited increase in contractility. In this study we compared the A2AR-, A1R-, and 131R-elicited actions on isolated rat ventricular myocytes in terms of Ca transient and contractile re- sponses involving PKA and PKC. Stimulation of A2AR with 2 p~M (-.~EC50) CGS-21680 (CGS) produced a 17-28% increase in the Ca transient ratio (CTR) and maximum velocities (Vm~,,~) of transient ratio increase (+MVT) and recovery (-MVT) but no change in the time-to-50% recovery (TTR). CGS increased myocyte sarcomere shortening (MSS) and the maximum velocities of shortening (+MVS) and relaxation (-MVS) by 31-34% with no change in time-to-50% relengthening (TTL). ~1R stimulation using 2 nM (-~EC50) isopro- terenol (Iso) increased CTR, +MVT, and -MVT by 67-162% and decreased TTR by 43%. Iso increased MSS, +MVS, and -MVS by 153-174% and decreased TI'L by 31%. The A2AR and ~31R Ca transient and contractile responses were not additive. The PKA inhibitor Rp-adenosine 3' ,5 `-cyclic monophosphorothioate triethyla- monium salt prevented both the CGS- and Iso-elicited contractile responses. The PKC inhibitors chelerythrine and KJE1-l peptide (PKCe specific) prevented the antiadrenergic action of A1R but did not influence A2AR-mediated increases in contractile variables. The findings suggest that cardiac A2AR utilize cAMPIPKA like 31R, but the Ca transient and contractile responses are less in magnitude and not equally affected. Although PKC is important in the ~ R antiad- renergic action, it does not seem to play a role in A2AR-elicited Ca transient and contractile events. [ABSTRACT FROM AUTHOR]

PKG activator 8-(4-chlorophenylthio)-guanosine 3′,5′-cyclic monophosphate (CPT) at reperfusion protects ischemic hearts, but the mechanism is unknown. We recently proposed that in preconditioned hearts PKC lowers the threshold for adenosine to initiate signaling from low-affinity A2b receptors during early reperfusion thus allowing endogenous adenosine to activate survival kinases phosphatidylinositol 3-kinase (PI3K) and ERK. We tested whether CPT might also sensitize A2b receptors to adenosine. CPT (10 µM) during the first minutes of reperfusion markedly reduced infarction in isolated rabbit hearts undergoing 30-min regional ischemia/2-h reperfusion, and salvage was blocked by MRS 1754, an A2b-selective antagonist. Coadministration of wortmannin (PI3K inhibitor) or PD-98059 (MEK1/2 and therefore ERK1/2 inhibitor) also blocked protection. In nonischemic hearts, 10-min infusion of CPT did not change phosphorylation of Akt or ERK1/2. Neither did a subthreshold dose (2.5 nM) of the nonselective but A2b-potent receptor agonist 5′-(N-ethylcarboxamido)adenosine (NECA). However, when 2.5 nM NECA was combined with 10 µM CPT, both phospho-Akt and phospho-ERK1/2 significantly increased, indicating CPT had lowered the threshold for Am-dependent signaling. The PKC antagonist chelerythrine blocked this phosphorylation induced by CPT + NECA. Chelerythrine also blocked the anti-infarct effect of CPT as did nonselective (glibenclamide) and mitochondrial-selective (5-hydroxydecanoate) KATP channel blockers. A free radical scavenger, N-(2-mercaptopropionyl)glycine, also blocked CPT protection. We propose CPT targets PKG, which activates PKC through mitochondrial KATP channel (mitoKATP)-dependent redox signaling, a sequence mimicking that already documented in preconditioning. Activated PKC then augments sensitivity of normally low-affinity cardiac adenosine A2b receptors so endogenous adenosine can protect by activating Akt and ERK. [ABSTRACT FROM AUTHOR]

The involvement of ecto-5′-nucleotidase (E-5′Nu) in the elevation of extracellular adenosine during inflammation is unclear. In the present study, the effect of lipopolysaccharide (LPS), an inflammation inducer, was investigated on E-5′Nu in human umbilical vein endothelial cells (HUVECs). E-5′Nu activity was enhanced after a 24 h exposure to LPS. This effect was dose dependent, with an EC50 of 1.66 ng/ml. At 10 µM, the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002 abolished the LPS-induced E-5′Nu activity. However, at 10 µM, the NF-κB inhibitor ammonium pyrrolidine dithiocarbamate had no effect. LPS upregulated the protein expression but not the messenger RNA expression of E-5′Nu. The inhibition of E-5′Nu by 100 µM α,β-methylene adenosine-5′-diphosphate increased the LPS-induced inflammation, suggesting that E-5′Nu plays a significant role in reducing inflammation, probably through the generation of adenosine. In conclusion, the experiments indicate that LPS upregulates E-5′Nu activity in HUVECs through a PI3K-dependent increase in the abundance of E-5′Nu on cell membranes. Since adenosine is an anti-inflammatory molecule, E-5′Nu upregulation may be crucial in protecting endothelial cells against inflammatory damage. [ABSTRACT FROM AUTHOR]

Cholesterol is a primary constituent of the plasmalemma, including the lipid rafts/caveolae, where various G protein-coupled receptors cobcalize with signaling proteins and channels. By manipulating cholesterol in rabbit and rat ventricular myocytes using methyl-β-cyclodextrin (MβCD), we studied the role of cholesterol in the modulation of L-type Ca2+ currents (ICa.L). MβCD was mainly dialyzed from BAPTA-containing pipette solution during whole cell clamp. In rabbit myocytes dialyzed with 30 mM MβCD for 10 min, a positive shift in membrane potential at half-maximal activation (V0.5) from -8 to -2 mV developed and was associated with an increase in current density at positive potentials (42% at +20 mV vs. time-matched controls). Isoproterenol (ISO) increased ICa.L approximately threefold and caused a negative shift in V0,5 in control cells, but it did not increase ICa.L in MβCD-treated myocytes, nor did it shift V0.5. The effect of MβCD (10 or 30 mM) was concentration dependent: 30 mM MβCD suppressed the ISO-induced increase in ICa.L more effectively than 10 mM MβCD. MβCD dialysis also abolished the increase in ICa.L elicited by forskolin or dibutyryl cAMP, but not that elicited by (-)BAY K 8644. External application of MβCD-cholesterol complex to rat myocytes attenuated the MβCD-mediated inhibition of the ISO-induced increase of ICaL. Biochemical analysis confirmed that the myocytes' cholesterol content was diminished by MβCD and increased by MβCD-cholesterol complex. Cholesterol thus appears to contribute to the regulation of basal ICa.L and β-adrenergic cAMP/PKA-mediated increases in ICa.L. We suggest that cholesterol affects the structural coupling between L-type Ca2+ channels and adjacent regulatory proteins. [ABSTRACT FROM AUTHOR]

To determine whether A1 adenosine receptors (AR) participate in adenosine-induced changes of coronary flow, isolated hearts from A1AR-/- and A1AR+/+ mice were perfused under constant pressure, and the effects of nonselective and selective agonists were examined. Adenosine, 5′-N-ethylcarboxamidoadenosine (NECA, nonselective), and the selective A2AAR agonist 2-2-carboxyethylphenethylamino-5′-N-ethylcarboxamidoadenosine (CGS-21680) augmented maximal coronary vasodilation in A1AR-/- hearts compared with A1AR+/+ hearts. Basal coronary flow was increased (P < 0.05) in A1AR-/- hearts compared with A1AR+/+ hearts: 2.548 ± 0.1 vs. 2.059 ± 0.17 ml/min. In addition, selective activation of A1AR with 2-chloro-N6-cyclopentyladenosine (CCPA) at nanomolar concentrations (1–100 nM) did not significantly change coronary flow; at higher concentrations, CCPA increased coronary flow in A1AR-/- and A1AR+/+ hearts. Because deletion of A1AR increased basal coronary flow, it is speculated that this effect is due to removal of an inhibitory influence associated with A1AR. Adenosine and NECA at approximately EC50 (100 and 50 nM, respectively) increased coronary flow in A1AR+/+ hearts to 177.86 ± 8.75 and 172.72 ± 17% of baseline, respectively. In the presence of the selective A1AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 50 nM), the adenosine- and NECA-induced increase in coronary flow in A1AR+/+ hearts was significantly augmented to 216.106 ± 8.35 and 201.61 ± 21.89% of normalized baseline values, respectively. The adenosine- and NECA-induced increase in coronary flow in A1AR-/- hearts was not altered by DPCPX. These data indicate that A1AR may inhibit or negatively modulate coronary flow mediated by other AR subtypes (A2A and A2B). [ABSTRACT FROM AUTHOR]

The etiology of the atherosclerosis that occurs in diabetes mellitus is unclear. Adenosine has been shown to inhibit growth of rat aortic smooth muscle cells. Nucleoside transporters play an integral role in adenosine function by regulating adenosine levels in the vicinity of adenosine receptors. Therefore, we studied the effect of 25 mM D-glucose, which mimics hyperglycemia of diabetes, on adenosine transport in cultured human aortic smooth muscle cells (HASMCs). Although RT-PCR demonstrated the presence of equilibrative nucleoside transporter-1 (ENT-1) and ENT-2 mRNA, functional studies revealed that adenosine transport in HASMCs was predominantly mediated by ENT-1 and inhibited by nitrobenzylmercaptopurine riboside (NBMPR, IC50 = 0.69 ± 0.05 nM). Adenosine transport in HASMCs was increased by >30% after treatment for 48 h with 25 mM D-glucose, but not with equimolar D-mannitol and L-glucose. Kinetic studies showed that D-glucose increased Vmax of adenosine transport without affecting Kin. Similarly, D-glucose increased Bmax of high-affinity [³H]NBMPR binding, while the dissociation constant (Kδ) was not changed. Consistent with these observations, 25 mM D-glucose increased mRNA and protein expression of ENT-1. Treatment of serum-starved cells with the selective inhibitors of MAPK/ERK, PD-98059 (40 μM) and U-0126 (10 μM), abolished the effect of D-glucose on ENT-1. We conclude that D-glucose upregulates the protein and message expression and functional activity of ENT-1 in HASMCs, possibly via MAPK/ERK-dependent pathways. Pathologically, the increase in ENT-1 activity in diabetes may affect the availability of adenosine in the vicinity of adenosine receptors and, thus, alter vascular functions in diabetes. [ABSTRACT FROM AUTHOR]

Gender influences volume regulation via several mechanisms; whether these include microvascular exchange, especially in the heart, is not known. In response to adenosine (Ado), permeability (Ps) to protein of coronary arterioles of female pigs decreases acutely. Whether Ado induces similar Ps changes in arterioles from males or whether equivalent responses occur in coronary venules of either sex has not been determined. Hypotheses that I) basal Ps properties and 2) Ps responses to vasoactive stimuli are sex independent were evaluated from measures of Ps to two hydrophilic proteins, α-lactalbumin and porcine serum albumin (PSA), in arterioles and venules isolated from hearts of adult male and female pigs. Consistent with hypothesis 1, basal Ps values of both microvessel types were independent of sex. Contrary to hypothesis 2, Ps responses to Ado varied with sex, protein, and vessel type. Confirming earlier studies. Ado induced a ∼20% decrease in P to both proteins in coronary arterioles from females. In arterioles from males, Ado did not change Ps for α-lactalbumin (pα-lactalb 3 ± 13%), whereas Ps for PSA (PsPSA) decreased by 27 ± 8% (P < 0.005). In venules from females, Ado elevated PsPSA by 44 ± 20% (P < 0.05), whereas in those from males, Ado reduced psPSA by 24 ± 5% (P < 0.05). The variety of outcomes is consistent with transvascular protein and protein-carried solute flux being regulated by multiple sex-dependent mechanisms in the heart and provides evidence of differences in exchange homeostasis of males and females in health and, likely, disease. [ABSTRACT FROM AUTHOR]

Adenosine is a key myocardial metabolite that elicits coronary vasodilation in a variety of pathophysiological conditions. We examined the mechanism of adenosine-induced vasodilation in coronary arterioles from patients with heart disease. Human coronary arterioles (HCA5) were dissected from pieces of the atrial appendage obtained at the time of cardiac surgery and cannulated for the measurement of internal diameter with videomicroscopy. Adenosine-induced vasodilation was not inhibited by endothelial denudation, but A2 receptor antagonism with 3,7-dimethyl-1-propargylxanthine and adenylate cyclase (AC) inhibition with SQ22536 significantly attenuated the dilation. In contrast, A1 receptor antagonism with 8-cyclopentyl-1,3-dipropylxanthine significantly augmented the sensitivity to adenosine. Moreover, dilation to A2a receptor activation with 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride was reduced by the A1 receptor agonist (2S)-N6-(2-endo-norbornyl)adenosine. The nonspecific calcium-activated potassium (KCa) channel blocker tetrabutylammonium attenuated adenosine-induced dilation, as did the intermediate-conductance KCa blocker clotrimazole. Neither the large-conductance KCa blocker iberiotoxin nor small-conductance KCa blocker apamin altered the dilation. In conclusion, adenosine endothelium independently dilates HCAs from patients with heart disease through a receptor-mediated mechanism that involves the activation of intermediate-conductance KCa channels via an AC signaling pathway. The roles of A1 and A2 receptor subtypes are opposing, with the former being inhibitory to AC-mediated dilator actions of the latter. These observations identify unique fundamental physiological characteristics of the human coronary circulation and may help to target the use of novel adenosine analogs for vasodilation in perfusion imaging or suggest new strategies for myocardial preconditioning. [ABSTRACT FROM AUTHOR]

Although acute adenosine preconditioning (PC) is well established, the signaling pathways mediating this cardioprotection remain unclear. Because adenosine receptor agonists activate p38 MAPK and this kinase has been implicated in ischemic and pharmacological PC, the purpose of this study was to determine the role of p38 MAPK in acute adenosine receptor PC. The role of p38 MAPK activation in discrete subcellular compartments during ischemia-reperfusion was also determined. The following groups were used in an in vivo rat ischemia-reperfusion model: 1) control (10% DMSO iv), 2) the A1/A2a adenosine receptor AMP-579 (50 μg/kg iv), 3) AMP-579 + the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 μg/kg iv), 4) AMP-579 + the p38 MAPK inhibitor SB-203580 (1 mg/kg iv), and 5) SB-203580 alone. p38 MAPK activation was measured by Western blot analysis in cytosolic, mitochondrial, membrane, and nuclear/myofilament fractions obtained from hearts at preischemic, ischemic, and reperfusion time points. A significant reduction in infarct size was observed with AMP-579 PC, an effect blocked by DPCPX or SB-203580 pretreatment. AMP-579 treatment was associated with a significant increase in p38 MAPK activation in the nuclear/myofilament fraction before ischemia, whereas no activation of this kinase occurred during ischemia or reperfusion. In contrast, p38 MAPK was activated in the mitochondrial fraction by ischemia and in the cytosolic, mitochondrial, and membrane fractions by reperfusion in the control group. SB-203580 blocked the AMP-579-induced increase in phosphorylation of the downstream p38 substrate activating transcription factor-2. These results suggest a role for p38 MAPK activation in discrete subcellular compartments in acute adenosine A1 receptor PC. [ABSTRACT FROM AUTHOR]

Presents information on a study that investigated inotropic effects of acetylcholine and adenosine on ferret ventricular cells with the action potential-clamp technique. Methodology of the study; Results and discussion on the study.

Discusses a study that determined whether adenosine (A[sub2a]) receptors are expressed in rat ventricular myocytes. Physiological effects that are mediated via activation of adenosine receptors; Method used to investigate the presence of A[sub2a] receptors in cells; Results and discussion.

Focuses on a study that examined coronary vascular and functional responses to adenosine and its analogs to clarify the roles of A[sub2] adenosine receptor subtypes in the regulation of coronary flow and myocardial contractility. Background on the cardiovascular effects of adenosine; Methods used; Results and discussion.

Presents a study which compared the vascular effects of adenosine on the heart and aorta of an isolated mouse. Characteristics of responses to adenosine and its analogs in the coronary and aortic vasculature; Adenosine receptor subtypes involved in the effects using different antagonist; Methodology and discussion.

Presents a study which tested the hypothesis that adenosine receptor blockade by caffeine would attenuate reflex muscle sympathetic nerve activity responses to handgrip and posthandgrip ischemia. Methods; Results; Discussion.

Presents a study which tested the hypothesis that adenosine triphosphate released in response to reduced dioxide levels serves as a source of adenosine. Methods; Results; Discussion.

Presents a study which determined whether the delayed cardioprotective effects of adenosine A[sub 1] or A[sub 3] receptors in late ischemic preconditioning are mediated by cyclooxygenase-2. Methodology; Results; Discussion.

Presents a study which determined the role of of A[sub 1] agonist 8-cyclopentyl-1,3,-dipropylxanthine in adenosine A[sub 1] agonist cardioprotection. Methodology; Results; Discussion.

Presents information on a study which evaluated the effectiveness of adenosine receptors in preventing ischemia-reperfusion skin injury and ulcer formation. Materials and methods; Results of the study; Discussion.

Presents a study which examined the role of adenosine in vascular contractile preconditioning. Methodology; Results; Discussion.

Presents information on a study which investigated the role of adenosine in the mediation of coronary and aortic smooth muscle dilation, and the effect of age on the process. Methodology; Results of the study; Discussion.

Presents information on a study which investigated cell receptor subtypes that mediate the dilation of cerebral arterioles elicited by adenosine. Methodology; Results of the study; Discussion.

Provides information on a study which investigated the role of p38 mitogen-activated protein kinase phosphorylation and opening of the mitochondrial adenosine triphosphate-sensitive potassium ion channel in the adenosine receptor-induced delayed cardioprotective effect in the mouse heart. Methods used in the study; Results and discussion.

Deals with a study which investigated the role of adenosine triphosphatase-sensitive potassium channels, nitric oxide, and adenosine in coronary exercise hyperemia. Methods; Results; Discussion.

Features a study which determined the effects of CVT-2759, a potential partial agonist of A[sup 1]-adenosine receptors on guinea pig hearts. Details on A[sup 1]-adenosine receptors; Methodology; Results; Discussion.

Presents a study which determined whether adenosine-enhanced ischemic preconditioning is modulated by adenosine triphosphate (ATP)-sensitive potassium channels. Mechanism of action of sarcolemmal and mitochondrial ATP-sensitive potassium channels during myocardial ischemia and reperfusion; Methodology; Results and discussion.

Presents a study which determined the possible link among adenosine receptors, phosphoinositide-protein kinase C (PKC) signaling and velocity in rat ventricular myocytes. Methodology; Results; Discussion.

Presents a study which examined the coronary arteriolar dilation response to adenosine and to adenosine triphosphate-sensitive potassium channel activation at various intraluminal pressure. Methodology; Results; Discussion.

Presents a study which examined whether adenosine-induced preconditioning reduces the vasoconstrictive effect of endothelin-1 on coronary arterioles. Identification of the adenosine receptor involved in ischemic preconditioning; Methodology; Results and discussion.

Presents information on a study which investigated the mechanism of adenosine-induced vasodilation in rat diaphragm microcirculation using laser Doppler flowmetry. Methodology of the study; Results and discussion on the study.

Presents information on a study which assessed the role of A...adenosine receptor activation by endogenous adenosine in the modulation of ischemic contracture and postischemic recovery in Langendorff-perfused mouse hearts subjected to ischemia and reperfusion. Methodology of the study; Results and discussion on the study.

Presents information a study which tested whether increased endogenous adenosine produced by the adenosine kinase inhibitor GP-515 can induce vascular endothelial growth factor expression in cultured rat myocardial myoblasts. Methodology of the study; Results and discussion on the study.

Presents a study which investigated adenosine transport in coronary smooth muscle. Adenosine in the enhancement of vasorelaxation; Adenosine transport; Account of related studies; Methodology of the study; Discussion of the results.

Presents a study which investigated the role of A... adenosine receptors in ischemic preconditioning. Materials and methods; Results; Discussion.

Reports a study which determined whether the protective effects of adenosine on myocardial ischemia-reperfusion injury are altered with age and clarified the mechanisms that underlie the change related to nitric oxide (NO) derived from the vascular endothelium. Cardioprotective effects of adenosine; Effects of adenosine on NO; Effect of NO synthesis blockade on the cardioprotective action of adenosine in adult hearts.

Presents a study which measured the adenosine-induced changes in contractile tension and myoplasmic free calcium concentration in collateral-dependent and nonoccluded coronary arteries isolated from sedentary control and exercise-trained pigs. Methodology; Results and discussion; Conclusions.

Provides information on a study which analyzed the impact of age on functional sensitivity to A...-adenosine receptor activation in rats. Methods of the study; Results and discussion.

Presents information on a study which evaluated the role of adenosine in coronary blood flow in dogs during exercise. Surgical preparation; Materials and methods of the study; Results and discussion.

Examines the conductances for inosine (Ino) and adenosine (Ado) by the nucleoside transporter of cardiac capillary endothelial cells in the intact heart functioning in perfuso, using high-resolution multiple-indicator dilution (MID). Outflow dilution data for Ino and Ado; Ino outflow dilution data of rabbit; Ino outflow dilution data of guinea pigs.

Deals with a study which determined whether adenosine has a differential effect on vascular endothelial growth factor (VEGF) expression under normoxic and hypoxic conditions. VEGF protein expression in normoxia; Dose-related inhibition of VEGF expression; VEGF messenger RNA (mRNA) expression in normoxic and hypoxic conditions.

Examines whether coronary microembolization increases coronary blood flow (CBF) through adenosine release in anesthetized open-chest pigs. Effects on CBF by microembolization; Metabolic alterations by microembolization; Effects of CBF reserve by microembolization.

Deals with a study which tested whether stimulation of the adenosine A3 receptor with the highly selective A3 agonist 2-chloro-N...-(3-iodobenzyl)-adenosine-5-N-methyluronamid e (Cl-IB-MECA) would reduce postischemic dysfunction. Development of left ventricular pressure; Discussion on coronary perfusate flow; Cumulative effluent creatinine kinase.

Offers information on a study which examined the hemodynamic effects of adenosine ...-receptor agonists. Account of related studies; Materials and methods; Results and discussion.

Presents information on a study which investigated the inotropic action of adenosine receptor mediated by calcium dependent mechanism on cardiomyocyte shortening. Methodology used; Results and discussion; Conclusion.

Editorial. Presents information on a study which investigated the pathophysiological and physiological role of adenosine receptor subtypes in the heart. Expression and functions of various adenosine receptor subtypes; Approaches for overcoming the limitations imposed by the systemic hemodynamic effects of adenosine and adenosine receptor agonists.

Presents information on a study on the effect of decreased adenosine levels on cerebral vasodilation in a newborn pig. Information on convulsions as a manifestation of neonatal neurologic disorders; Methods used in the study; Results of the study.

Studies the effects of preconditioning and adenosine on neutrophil rolling and vascular dysfunction. Hemodynamic factors during ischemia-reperfusion (I/R); Effects of preconditioning on postischemic vasculature; Preconditioning and role of adenosine; Exogenous adenosine's effects on postichemic vasculature.

Determines whether stretch-induced preconditioning may be related to activation of adenosine receptors, ATP-sensitive potassium (K+ATP) channels and protein kinase C in the rabbit heart. Occurence of infarct-size-reducing effect of stretch in the absence of ischemia; Possible direct activation of K+ATP channels by mechanical deformation of myocyte.

Determines the localization and functional implications of adenosine A1 receptors on cardiac vagal afferents in adult rats. Production of adenosine; Radioreceptor assay; Receptor-labeling autoradiography; Cellular electrophysiology.