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Adenosine and adenosine triphosphate antagonise the isoprenaline induced [Na]o dependent inward current in guinea-pig ventricular myocytes
J Mol
Cell
Cad01
21 (Supplement
II) (1989)
130 ADENOSINE
RECEPTOR ANTAGONISM DOES NOT ALTER FREE-FLOW EXERCISE HYPEREMIA IN CONSCIOUS DOGS. P.J. Metting, L.G. Koch, D.M. Strick, S.L. Britton. Department of Physiology, Medical College of Ohio, Toledo, Ohio 43699. Although it is well accepted that adenosine contributes to exercise-induced vasodilation under ischemic or hypoxic conditions, the role of adenosine in free-flow exercise hyperemia remains unresolved. Previous studies have been conducted in anesthetized animals in which exercise was simulated by electrical stimulation of skeletal muscles; under these conditions the results were equivocal. Therefore, the purpose of this project was to evaluate the contribution of endogenous adenosine to the increase in skeletal muscle blood flow that is known to occur during physiological exercise. Specifically, we tested the hypothesis that if adenosine is an important mediator of hindlimb vasodilation during free-flow exercise, then the level of exercise hyperemia should be decreased by antagonism of adenosine receptor sites with aminophylline. Standard Doppler or electromagnetic technology was employed to measure hindlimb blood flow (HLBF) in 16 conscious dogs studied with and without pretreatment with aminophylline. Steadystate HLBF was recorded between lo-15 min of treadmill exercise at a rate of 5.5 km/h and a grade of 7, 14, or 21%. Aminophylline did not decrease the level of exercise hyperemia at any of the 3 exercise intensities. These data indicate that adenosine is not essential for hindlimb vasodilation during free-flow exercise. (Supported by AHA, Ohio Affiliate)
131
REDUCED CORONARY EFFLUENT ADENOSINE RELEASE WITH B-ADRENERGIC STIHULATION OF THti NORWOTENSIY~LY PERFUSED SPONTANEOUSLY RYPERTENSIFK RAT (siikz) HEART. S.U. Rodin, J.G. Dobson, Jr., Dept. of Physiology, Univ. of Massachusetts, Worcester WA, 01655 USA Since adenosine (ADO) is known to have antiadrenergic and vasodilatory actions in the heart we undertook to determine whether the reduced cardiac contractile response of SHR to S-adrenergic stimulation is associated with an elevation of SHR and control Wistar Kyoto (W) hearts were perfused at 80 endogenous ADC levels. No difference was found in basal coronary effluent (CE) ADO release rates torr. (14.1 + 1.6 (W) vs. 10.2 + 2.1 umol/min/gdw (SHR)] or basal 0, supply:demand ratios il.42 + .04 (W) vs 1.31 + .lO (SHR)l. Stimulation with 10 nt4 isoproterenol (ISO) resulted in a smaller percentage increase in contractility in SHR [85% (W) vs 49x (sHR)]. During IS0 stimulation SHR appeared to be hypoxic compared to W as indicated by the significantly lower 0, supply:demand ratios Il.14 + .03 (W) the augmentation of CE ADO release by IS0 was vs 1.09 + .oi (sHR)). However, significantly reduced in SHR hearts t58.3 + 15.8(W) vs 21.0 f. 3.7 umol/min/gdw (sHR)]. Assuming that cardiac ADO sensitivity is unaltered, these data suggest that the depressed inotropic response to B-adrenergic activation of the normotensively perfused SHR heart is not attributable to the antiadrenergie action of In SHR the attenuation of ADO but may result, in part, from myocardial hypoxia. catecholamine-induced ADO release may limit the vasoregulatory contribution of ADO to the balance of oxygen supply to demand. (Supported by PH.9 HL-02186 6 HL-22828).
132
ADENOSINE AND ADENOSINE TRIPHOSPRATE ANTAGCNISE THE ISOPRRNALJNE INDUCED DEPENDENT INWARD CURRENT IN GUINEA-PIG VEX?TRICULAR MYCCYTES. R. [Ral Department of Medical Cardiology, Royal Site&esan, A.C. Rankin, K.A. Kane*. Infirmary; *Department of-Physiology & Pharmacology, University of Strathclyde, Glasgow, U.K. Using the whole cell patch clamp technique, the isoprenaline-induced dependent inward current (Egan et al., J. Phys., 1988, 400:299) and INal I $ere recorded in guinea-pig ventricular myocytes (36OC). &$erfueion of isoprenaline (l-1OOOnM) produced inward currents of 50-500pA which decreased with time in contrast to a maintained increase in I . This transient current was also induced by other agents which incre%e intracellular CAMP concentration, namely, histamine (50-4OOOnR), Adenosine isobutylmethylxanthine (30-1000@4) and theophyline (100@4). (lo-1000PM) and ATP (200,uM) antagonised the isoprenaline induced [Na] dependent inward current and the increase in I . The histamine effec ? s on and the transient inward current were simi .E"arly antagonised by dependent ki&osine. These results support the hypothesis that the [Na] This cur&t is blocked inward current is mediated via an increase in CAMP. ATP by adenosine, which can modulate the adenylate cyclase-cyclic AMP system. may have a similar effect, or may act via breakdown to adenosine. This work was supported by the Scottish Rome and Health Department. s.44
Cell
Cad01
21 (Supplement
II) (1989)
130 ADENOSINE
RECEPTOR ANTAGONISM DOES NOT ALTER FREE-FLOW EXERCISE HYPEREMIA IN CONSCIOUS DOGS. P.J. Metting, L.G. Koch, D.M. Strick, S.L. Britton. Department of Physiology, Medical College of Ohio, Toledo, Ohio 43699. Although it is well accepted that adenosine contributes to exercise-induced vasodilation under ischemic or hypoxic conditions, the role of adenosine in free-flow exercise hyperemia remains unresolved. Previous studies have been conducted in anesthetized animals in which exercise was simulated by electrical stimulation of skeletal muscles; under these conditions the results were equivocal. Therefore, the purpose of this project was to evaluate the contribution of endogenous adenosine to the increase in skeletal muscle blood flow that is known to occur during physiological exercise. Specifically, we tested the hypothesis that if adenosine is an important mediator of hindlimb vasodilation during free-flow exercise, then the level of exercise hyperemia should be decreased by antagonism of adenosine receptor sites with aminophylline. Standard Doppler or electromagnetic technology was employed to measure hindlimb blood flow (HLBF) in 16 conscious dogs studied with and without pretreatment with aminophylline. Steadystate HLBF was recorded between lo-15 min of treadmill exercise at a rate of 5.5 km/h and a grade of 7, 14, or 21%. Aminophylline did not decrease the level of exercise hyperemia at any of the 3 exercise intensities. These data indicate that adenosine is not essential for hindlimb vasodilation during free-flow exercise. (Supported by AHA, Ohio Affiliate)
131
REDUCED CORONARY EFFLUENT ADENOSINE RELEASE WITH B-ADRENERGIC STIHULATION OF THti NORWOTENSIY~LY PERFUSED SPONTANEOUSLY RYPERTENSIFK RAT (siikz) HEART. S.U. Rodin, J.G. Dobson, Jr., Dept. of Physiology, Univ. of Massachusetts, Worcester WA, 01655 USA Since adenosine (ADO) is known to have antiadrenergic and vasodilatory actions in the heart we undertook to determine whether the reduced cardiac contractile response of SHR to S-adrenergic stimulation is associated with an elevation of SHR and control Wistar Kyoto (W) hearts were perfused at 80 endogenous ADC levels. No difference was found in basal coronary effluent (CE) ADO release rates torr. (14.1 + 1.6 (W) vs. 10.2 + 2.1 umol/min/gdw (SHR)] or basal 0, supply:demand ratios il.42 + .04 (W) vs 1.31 + .lO (SHR)l. Stimulation with 10 nt4 isoproterenol (ISO) resulted in a smaller percentage increase in contractility in SHR [85% (W) vs 49x (sHR)]. During IS0 stimulation SHR appeared to be hypoxic compared to W as indicated by the significantly lower 0, supply:demand ratios Il.14 + .03 (W) the augmentation of CE ADO release by IS0 was vs 1.09 + .oi (sHR)). However, significantly reduced in SHR hearts t58.3 + 15.8(W) vs 21.0 f. 3.7 umol/min/gdw (sHR)]. Assuming that cardiac ADO sensitivity is unaltered, these data suggest that the depressed inotropic response to B-adrenergic activation of the normotensively perfused SHR heart is not attributable to the antiadrenergie action of In SHR the attenuation of ADO but may result, in part, from myocardial hypoxia. catecholamine-induced ADO release may limit the vasoregulatory contribution of ADO to the balance of oxygen supply to demand. (Supported by PH.9 HL-02186 6 HL-22828).
132
ADENOSINE AND ADENOSINE TRIPHOSPRATE ANTAGCNISE THE ISOPRRNALJNE INDUCED DEPENDENT INWARD CURRENT IN GUINEA-PIG VEX?TRICULAR MYCCYTES. R. [Ral Department of Medical Cardiology, Royal Site&esan, A.C. Rankin, K.A. Kane*. Infirmary; *Department of-Physiology & Pharmacology, University of Strathclyde, Glasgow, U.K. Using the whole cell patch clamp technique, the isoprenaline-induced dependent inward current (Egan et al., J. Phys., 1988, 400:299) and INal I $ere recorded in guinea-pig ventricular myocytes (36OC). &$erfueion of isoprenaline (l-1OOOnM) produced inward currents of 50-500pA which decreased with time in contrast to a maintained increase in I . This transient current was also induced by other agents which incre%e intracellular CAMP concentration, namely, histamine (50-4OOOnR), Adenosine isobutylmethylxanthine (30-1000@4) and theophyline (100@4). (lo-1000PM) and ATP (200,uM) antagonised the isoprenaline induced [Na] dependent inward current and the increase in I . The histamine effec ? s on and the transient inward current were simi .E"arly antagonised by dependent ki&osine. These results support the hypothesis that the [Na] This cur&t is blocked inward current is mediated via an increase in CAMP. ATP by adenosine, which can modulate the adenylate cyclase-cyclic AMP system. may have a similar effect, or may act via breakdown to adenosine. This work was supported by the Scottish Rome and Health Department. s.44