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Biomedical subjects

J M O'Donnell

Publications and source records attributed to J M O'Donnell.

At least 19 recordsLinked to original sources
PubMed1998

Dehydrogenase regulation of metabolite oxidation and efflux from mitochondria in intact hearts.

To test how alpha-ketoglutarate dehydrogenase (alpha-KGDH) activity influences the balance between oxidative flux and transmitochondrial metabolite exchange, we monitored these rates in isolated mitochondria and in perfused rabbit hearts at an altered kinetics (Km) of alpha-KGDH for alpha-ketoglutarate (alpha-KG). In isolated mitochondria, relative Km dropped from 0.23 mM at pH = 7.2 to 0.10 mM at pH 6.8 (P < 0.05), and alpha-KG efflux decreased from 126 to 95 nmol.min-1.mg-1. In intact hearts, Km was reduced with low intracellular pH, while matching control workload and respiratory rate with increased Ca2+ (pHi = 7.20, perfusate CaCl2 = 1.5 mM; pHi = 6.89, perfusate CaCl2 = 3 +/- 1 mM). Sequential 13C nuclear magnetic resonance spectra from hearts oxidizing [2-13C]acetate provided tricarboxylic acid cycle flux and the exchange rate between alpha-KG and cytosolic glutamate (F1). Tricarboxylic acid cycle flux was 10 mumol.min-1.g-1 in both groups, but F1 fell from a control of 9.3 +/- 0.6 to 2.8 +/- 0.4 mumol.min-1.g-1 at low Km. The results indicate that increased activity of alpha-KGDH occurs at the expense of alpha-KG efflux during support of normal workloads.

Acetates↗
PubMed1997

Degenerative changes in spermatogonia are associated with loss of glucose transporter (Glut 3) in abdominal testis of surgically induced unilateral cryptorchidism in rats.

Expression of facilitative glucose transporters (Glut 1, 2 and 3) was examined by Western blot analyses 10, 20 and 30 days following surgically induced unilateral abdominal cryptorchidism. The cryptorchid testes exhibited marked degenerative changes in the seminiferous tubules and spermatogonia, impaired and incomplete spermatogenesis and lack of spermatozoa in the lumen. Immunoblotting of testis proteins with Glut transporter antibodies revealed only the presence of Glut 2 and 3 proteins. Glut 2 expression in abdominal testis was increased (45%, 67%, and 40% at 10, 20 and 30 days, respectively) but no significant change was observed in contralateral scrotal testis. Glut 3 expression was reduced by 85-95% compared with contralateral scrotal testis. A significant decrease in Glut 3 levels in abdominal testis was accompanied by an increase in scrotal testis Glut 3 content (80%, 144% and 212% at 10, 20 and 30 days, respectively) compared to age matched control rats. These results suggested that the degenerative changes in abdominal testis may be associated with decreased Glut 3 mediated glucose transport in seminiferous tubules and spermatogonia.

Amino Acid Sequence↗
PubMed1997

Pharmacological characterization of the discriminative stimulus effects of clenbuterol in rats.

The beta-2 selective adrenergic agonist clenbuterol produces discriminative stimulus effects in rats. Administration of beta adrenergic agonists that do not cross the blood-brain barrier well following peripheral administration either failed to substitute for clenbuterol or resulted in chance levels of drug-appropriate responding; this suggested central mediation of the effects of clenbuterol. This interpretation was supported by the finding that the centrally acting beta adrenergic antagonist propranolol antagonized the discriminative stimulus effects of clenbuterol more potently than did CGP-12177, a hydrophilic beta adrenergic antagonist that has been shown to have very limited central activity. Antagonism experiments using subtype-selective antagonists showed that the beta-2 selective antagonist ICI 118,551 more potently antagonized the discriminative effects of the training dose of clenbuterol than did the beta-1 selective antagonist betaxolol. The present results indicate that the discriminative stimulus effects of clenbuterol provide an in vivo index of activation of central beta-2 adrenergic receptors.

Adrenergic beta-1 Receptor Agonists↗
PubMed1997

Noradrenergic activity differentially regulates the expression of rolipram-sensitive, high-affinity cyclic AMP phosphodiesterase (PDE4) in rat brain.

In a previous study, it was observed that the activity of rolipram-sensitive, low-Km, cyclic AMP phosphodiesterase (PDE4) was decreased in vivo with diminished noradrenergic stimulation. The results of the present experiments indicated that the reduction in the activity may be associated with down-regulation of PDE4 protein. Immunoblot analysis using PDE4-specific, subfamily-nonspecific antibody (K116) revealed four major bands of PDE4 in rat cerebral cortex; those with apparent molecular masses of 109 and 102 kDa are variants of PDE4A. Diminished noradrenergic activity, produced by intracerebroventricular infusion of 6-hydroxydopamine (6-OHDA) or chronic subcutaneous infusion of propranolol, decreased the intensities of the protein bands for the 109- and 102-kDa PDE4A variants in rat cerebral cortex but not of the 98- or 91-kDa PDE4 forms. 6-OHDA-induced noradrenergic lesioning also decreased the content of 102-kDa PDE4A in hippocampus as labeled by PDE4A-specific antibody (C-PDE4A). Enhanced noradrenergic stimulation up-regulated PDE4 in cerebral cortex. This was indicated by the finding that repeated treatment with desipramine increased the intensity of the protein band for the 102-kDa PDE4 but not for the other variants of PDE4. These results suggest that PDE4 subtypes are differentially regulated at the level of expression, as evidenced by an apparent change in the amount of PDE4 protein, following changes in noradrenergic activity. These observations are consistent with the notion that PDE4s, especially the PDE4A variants with molecular masses of 109 and 102 kDa, play an important role in maintaining the homeostasis of the noradrenergic signal transduction system in the brain and may be involved in the mediation of antidepressant activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Phosphorus-31 magnetic resonance spectroscopy studies of pig spinal cord injury. Myelin changes, intracellular pH, and bioenergetics.

RATIONALE AND OBJECTIVES: Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy was used to monitor changes in phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi), intracellular pH (pHi), and free magnesium in the in vivo pig spinal cord after injury. METHODS: Phosphorus-31 NMR spectra were acquired from healthy (n = 4) and injured pig spinal cords (n = 8) under in vivo conditions using a 4.7-tesla spectrometer. Spinal cords were injured by dropping a 20-g weight from 20 cm onto the surgically exposed cord surface. RESULTS: In vivo spectra of injured cords revealed a reduction in ATP, PCr, pHi, and an increase in Pi. In addition, a broad resonance that is likely to arise from myelin phospholipids was reduced significantly after injury. CONCLUSIONS: Phosphorus-31 NMR can be used to follow in vivo changes in high energy phosphates after injury and may have the potential to follow changes in myelin structure. This technique may prove important in the study of myelin breakdown after secondary, nonreversible spinal cord injury. Changes in high energy phosphates and pHi did not seem to parallel these putative changes in myelin structure.

Adenosine Triphosphate↗
PubMed1997

Altered metabolite exchange between subcellular compartments in intact postischemic rabbit hearts.

To examine metabolic regulation in postischemic hearts, we examined oxidative recycling of 13C within the glutamate pool (GLU) of intact rabbit hearts. Isolated hearts oxidized 2.5 mmol/L [2-13C]acetate during normal conditions (n = 6) or during reperfusion after 10 minutes of ischemia (n = 5). 13C-Nuclear magnetic resonance spectra were acquired every 1 minute. Kinetic analysis of 13C incorporation into GLU provided both tricarboxylic acid (TCA) cycle flux and the interconversion rate (F1) between the TCA cycle intermediate, alpha-ketoglutarate (alpha-KG), and the largely cytosolic GLU. The rate-pressure product in postischemic hearts was 46% of normal (P < .05). No difference in substrate utilization occurred between groups, with acetate accounting for 92% of the carbon units entering the TCA cycle at the citrate synthase step. TCA cycle flux in postischemic hearts was normal (normal hearts, 10.7 mumol.min-1.g-1; postischemic hearts, 9.4 mumol.min-1.g-1), whereas F1 was 72% lower at 2.9 +/- 0.4 versus 10.2 +/- 2.5 mumol.min-1.g-1 (mean +/- SE) in normal hearts (P < .05). From additional hearts perfused with 2.5 mmol/L [2-13C]acetate plus supplemental 5 mmol/L glucose, any potential differences in endogenous carbohydrate availability were proved not to account for the reduced rate alpha-KG and GLU exchange, which remained depressed in postischemic hearts. However, specific activities of the transaminase enzyme, catalyzing chemical exchange of alpha-KG and GLU, were the same, and transaminase flux was 100 mumol.min-1.g-1 in postischemic hearts versus 68 mumol.min-1.g-1 in normal hearts. Normal transaminase activity and the increased flux in postischemic hearts are contrary to the reduced F1. The findings indicate reduced metabolite transport rates across the mitochondrial membranes of stunned myocardium, particularly through the reversible alpha-KG-malate carrier.

Animals↗
PubMed1997

Antisense oligonucleotides fail to inhibit the expression of central beta adrenergic receptors.

A number of antisense phosphorothioate oligodeoxynucleotides (ODNs) targeted to different regions of mRNAs were tested for their ability to inhibit the expression of central beta adrenergic receptors (ARs). None of these antisense ODNs reduced beta AR density. By contrast, a dopamine D2 receptor antisense ODN did decrease striatal D2 receptor density. The recovery of beta AR density after down-regulation was not altered by any of the antisense ODNs tested. Moreover, the response of rats under a DRL 72-sec schedule to clenbuterol, a beta-2 selective AR agonist, was not attenuated by chronic treatment with a beta-2 AR antisense ODN.

Adrenergic beta-Agonists↗
PubMed1996

Diminished noradrenergic stimulation reduces the activity of rolipram-sensitive, high-affinity cyclic AMP phosphodiesterase in rat cerebral cortex.

The present study examined the in vivo regulation of rolipram-sensitive, high-affinity cyclic AMP phosphodiesterase (PDE4) in rat cerebral cortex. The hydrolysis of cyclic AMP, formed by stimulation of beta-adrenergic receptors, was measured in cerebral cortical slices. Hydrolysis of cyclic AMP formed under these conditions was inhibited by the PDE4-selective inhibitor rolipram but not by selective inhibitors of other PDE families. Intraventricular infusion of 6-hydroxydopamine (6-OHDA; 200 micrograms) decreased the rate constant of cyclic AMP hydrolysis and increased the cyclic AMP half-life 17 days, but not 1 or 7 days, following the treatment. A reduction in norepinephrine (NE) content occurred first; the NE level was reduced to 42, 24, and 6% of control at 1, 7, and 17 days after 6-OHDA infusion, respectively. This was followed by the development of supersensitivity of beta-adrenergic receptor-linked adenylyl cyclase, which occurred 7 days after the infusion. The reduction in PDE4 activity occurred last. When a higher dose of 6-OHDA (300 micrograms) was used, the reduction in the rate constant of cyclic AMP hydrolysis occurred by 7 days; at this time NE content was depleted to 6% of control. Similar to 6-OHDA treatment, continuous blockade of beta-adrenergic receptors, produced by chronic propranolol infusion, decreased the rate constant of cyclic AMP hydrolysis. Therefore, the current results indicate that diminished stimulation of beta-adrenergic receptors, either by loss of noradrenergic innervation or by receptor blockade, reduces the activity of PDE4. This suggests that PDE4 regulation may contribute in the homeostasis of the noradrenergic receptor-effector system in the brain.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Phosphorus-31 nuclear magnetic resonance spectroscopy of the spinal cord in the pig, rat, and rabbit.

RATIONALE AND OBJECTIVES: To ensure that contamination-free phosphorus-31 nuclear magnetic resonance (31P-NMR) spectra of the spinal cord could be obtained, a porcine model was adopted that provided a large cord sample and a greater area free from adjacent muscle tissue. METHODS: Phosphorus-31 NMR spectra were acquired from the porcine spinal cord under in vivo conditions using a 4.7-T spectrometer. Spectra also were collected from perchloric acid and lipid extracts, and excised freeze trapped samples of the rat, rabbit, and pig spinal cord. RESULTS: The in vivo spectrum showed resonances corresponding to adenosine triphosphate, phosphocreatine, inorganic phosphate, phosphomonoesterase, and phosphodiesterase as confirmed by extracts. In addition, a broad resonance was observed that was assigned to myelin phospholipids. CONCLUSION: Phosphorus-31 NMR spectra of the spinal cord revealed resonances common to brain tissue. Importantly, the existence of a previously undetected resonance, which is likely to correspond to myelin phospholipids, also is reported. This resonance may prove important in future studies monitoring changes in myelin in response to trauma and ischemia.

Animals↗
PubMed1996

Altered thermoregulatory responses to clonidine in streptozotocin-diabetic rats.

1. The effects of streptozotocin (STZ) treatment on alpha 2-adrenoceptor regulation of body temperature were studied by monitoring the response of colonic temperature to administration of clonidine. 2. A dose-dependent fall in colonic temperature occurred in control rats given clonidine challenge (0.05-2.0 mg kg-1, s.c.); this response was inhibited by prior administration of either yohimbine or idazoxan (2 mg kg-1, s.c.) but not by the peripherally-acting alpha 2-adrenoceptor antagonist L-659,066 (10 mg kg-1, s.c.). 3. In rats treated with STZ (65 mg kg-1, i.v.) administration of clonidine elicited a dose-independent hyperthermia (circa 1 degree C.); this effect was unaltered by prior administration of yohimbine or idazoxan. 4. Naloxone (5 mg kg-1, s.c.) elicited a small fall in temperature (< 1 degree C.) in both control and STZ-treated rats; naloxone pretreatment did not alter the temperature response to clonidine in either group. 5. Nicotinic acid (10 mg kg-1, s.c.) caused a similar small elevation in temperature in both groups. 6. Administration of replacement insulin to STZ-treated rats maintained weight gain and low blood glucose while the thermoregulatory response to clonidine slowly reverted to normal. 7. These results show that altered central temperature control is an element of the generalised abnormality of alpha 2-receptor function induced by STZ.

Adrenergic alpha-Agonists↗
PubMed1995

Facilitation of noradrenaline release from rat brain slices by beta-adrenoceptors.

The present study examined whether stimulation of beta-adrenoceptors facilitated noradrenaline release in the rat brain. Electrical stimulation-evoked overflow of tritium from rat cerebral cortical, hypothalamic and hippocampal slices labelled with 3H-noradrenaline was measured during superfusion for 100 min. Tissue slices were electrically simulated (1 Hz, 20 mA, 2 ms, 2 min), at 20 (S1) and 70 (S2) min after the onset of superfusion. The nonselective beta-adrenoceptor agonist isoproterenol (0.1-10 nM) enhanced stimulation-evoked overflow of tritium from slices of cerebral cortex, hypothalamus and hippocampus in a concentration-dependent manner; mean S2/S1 ratios with 10 nM isoproterenol were 161 +/- 11%, 142 +/- 15% and 143 +/- 12% of control, respectively, in the three brain regions. The facilitatory effect of isoproterenol in cerebral cortical slices was antagonized by propranolol (50 nM), a nonselective beta-adrenoceptor antagonist, and by the beta 1- and beta 2-selective adrenoceptor antagonists ICI 89,406 (1 nM) and ICI 118,551 (1 nM), respectively. The beta 1- and beta 2-selective adrenoceptor agonists prenalterol and albuterol (0.1-10 nM), respectively, also increased stimulation-evoked overflow of tritium from cerebral cortical slices; these effects were antagonized by beta-adrenoceptor antagonists. These findings suggest that stimulation of beta-adrenoceptors enhance noradrenaline release from rat cerebral cortical, hypothalamic and hippocampal slices; this release mechanism appears to involve both beta 1- and beta 2-adrenoceptor subtypes. These facilitating presynaptic receptors may be involved in mediating the antidepressant-like behavioral effects of beta 2-adrenoceptor agonists.

Albuterol↗
PubMed1995

Facilitation of norepinephrine release from cerebral cortex is mediated by beta 2-adrenergic receptors.

Facilitatory effects of prenalterol and albuterol (beta 1- and beta 2-selective adrenergic agonists, respectively) in the absence and presence of propranolol (a nonselective beta-adrenergic antagonist), ICI 89,406 or ICI 118,551 (beta 1- and beta 2-selective adrenergic antagonists, respectively) on electrical stimulation-evoked release of 3H-NE from rat cerebral cortical slices were assessed. Albuterol (0.1-100 nM) increased evoked release of 3H-NE from the cerebral cortical slices with greater potency than prenalterol (1-100 nM). The beta 2-adrenergic antagonist ICI 118,551 (1 nM) and propranolol (50 nM) abolished the facilitatory effects of albuterol (0.1 and 10 nM). In contrast, the beta 1-adrenergic antagonist ICI 89,406 (1 nM) did not alter the release-enhancing effect of albuterol. Prenalterol (10 and 100 nM)-induced facilitation of evoked release of 3H-NE was abolished by ICI 118,551; propranolol reduced the effect of 10 nM prenalterol and abolished that of 100 nM prenalterol. ICI 89,406 inhibited the effect of 100 nM prenalterol without altering that of 10 nM prenalterol. Basal release of 3H-NE was not altered by the drugs used in this study. These results suggest that facilitation of 3H-NE release induced by beta-adrenergic agonists is mediated primarily by beta 2-adrenergic receptors.

Adrenergic beta-Agonists↗
PubMed1995

Cardiac beta-adrenoceptor-effector coupling in portal vein-stenosed rats.

Cardiac beta-adrenergic signal transduction was examined in chronic portal vein-stenosed rats. Basal tension and maximum rate of tension development were significantly depressed in left ventricular papillary muscles (0.21 +/- 0.03 N/cm2 and 8.2 +/- 1.7 N.s-1.cm-2, respectively) compared with sham-operated controls (0.51 +/- 0.05 N/cm2 and 19.9 +/- 4.4 N.s-1.cm-2, respectively). The positive inotropic response to isoproterenol was also attenuated. Adenosine 3',5'-cyclic monophosphate formation was decreased significantly when GTP (-41.9%), isoproterenol with GTP (-45.3%), or guanosine 5'-O-(3-thiotriphosphate) (-52.4%) was used to stimulate adenylyl cyclase, but not when Mn2+ or forskolin was used. Beta-Adrenoceptor density (sham operated 24.6 +/- 2.0 fmol/mg; portal vein stenosed 26.4 +/- 2.1 fmol/mg) and the apparent dissociation constant (sham operated 0.26 +/- 0.04 nM; portal vein stenosed 0.29 +/- 0.04 nM) were unaffected. Portal venous hypertension did not alter beta-adrenergic receptor affinity for isoproterenol. However, it was necessary for isoproterenol to occupy three times the number of receptors in papillary muscles from stenosed animals to produce an equal increase in force generation. These data suggest that although portal vein stenosis does not alter cardiac beta-adrenoceptor density or affinity for ligands, transduction of the signal between the receptor and adenylyl cyclase is adversely influenced and may be responsible for the diminished responsiveness of beta-adrenoceptors in the myocardium.

Adenylyl Cyclases↗
PubMed1995

Orotracheal tube intracuff pressure initially and during anesthesia including nitrous oxide.

Certified Registered Nurse Anesthetists (CRNA) have an ethical obligation to assure the safety of the anesthetized patient. Maintenance of orotracheal tube intra-cuff pressure (IcP) in a range preventing aspiration and avoiding tracheal ischemia is one way to enhance patient safety. Currently, no standardized method of cuff inflation and IcP maintenance is used in anesthesia practice. In addition, nitrous oxide (N2O) has the ability to diffuse into and inflate a cuff. Rate of N2O induced cuff inflation in vivo, has not been clearly delineated in the current literature. This study measured IcP initially, and over time during an anesthetic including 50% to 70% N2O. The sample consisted of 44 adult subjects intubated orally. Cuff inflation technique was identified and initial IcPs were recorded. IcP was then adjusted to 19 mm Hg and was continuously monitored until increasing to 25 mm Hg. A variety of cuff inflation methods were observed none of which consistently achieved an initial IcP within the target range of 19 to 25 mm Hg. IcP rose from 19 to 25 mm Hg in all cases during N2O administration. Elapsed time for the IcP increase ranged from 2 to 52 minutes (mean = 12.34, median = 8 minutes). During anesthesia with 50% to 70% N2O, IcP will increase from initial safe levels to ischemia producing levels. Devices and approaches designed to limit N2O induced IcP increase have been described, however only direct IcP monitoring has been shown to assure safe initial and ongoing IcP.

Adult↗
PubMed1995

Beta adrenergic receptors facilitate norepinephrine release from rat hypothalamic and hippocampal slices.

Basal and electrical stimulation-induced release of tritiated norepinephrine (3H-NE) was determined in superfused slices of the rat hypothalamus and hippocampus. Isoproterenol (0.1-10 nM), a nonselective beta-adrenergic agonist, enhanced stimulation-evoked release of 3H-NE from hypothalamic and hippocampal slices in a concentration-dependent manner without consistently altering basal release. Isoproterenol (1 nM) increased ratios of S2/S1 to 143 +/- 4% (hypothalamus) and 152 +/- 15% (hippocampus) of control values. The facilitatory effects of isoproterenol were antagonized by propranolol (50 nM), a nonselective beta-adrenergic antagonist. The beta 2-selective adrenergic agonist clenbuterol (10-100 microM) enhanced basal release of 3H-NE in a concentration-dependent fashion. These results provide evidence for a beta-adrenergic receptor mediated regulation of NE release from hypothalamic and hippocampal slices. Whether the positive feedback mechanism contributes to any of the NE-mediated physiological functions associated with the hypothalamus and hippocampus requires further study. However, the effect of clenbuterol indicates that some of its behavioral actions in animals may be attributed to this NE release-enhancing effect observed in the present study.

Adrenergic beta-2 Receptor Agonists↗
PubMed1994

A maternal product of the Punch locus of Drosophila melanogaster is required for precellular blastoderm nuclear divisions.

The Punch locus of Drosophila melanogaster encodes the pteridine biosynthesis enzyme guanosine triphosphate cyclohydrolase. One class of Punch mutants is defective for a maternal function that results in embryonic death. We demonstrate here that the embryos exhibit nuclear division defects during the precellular blastoderm stage of development. These defects include abnormal nuclear distribution, mitotic asynchrony, and persisting chromatin bridges. Daughter nuclei that do not complete chromosome separation nevertheless initiate new interphase and mitotic cycles. As a result, interconnected mitotic figures are observed. Mitotic spindles and nuclear envelopes appear essentially normal. A mutant phenocopy was induced in wild-type embryos by treatment with the guanosine triphosphate cyclohydrolase inhibitor, 2,4-diamino-6-hydroxypyrimidine, at a very early cleavage stage. Furthermore, an inhibitor of a terminal step in pteridine biosynthesis produced an identical phenotype. Immunolocalization experiments define expression of Punch protein in nurse cells during oogenesis. The protein is packaged into granules as it is transported into the oocyte cytoplasm. As syncytial blastoderm nuclear divisions proceed, Punch protein levels decrease and disappear by cellularization. Defects in the expression of the protein in Punch maternal effect mutants correlate well with the early phenotypes. These results show that a Punch product is directly involved in early nuclear divisions and suggest a possible role in chromosome separation.

Animals↗
PubMed1994

Clenbuterol increases norepinephrine release from rat brain slices by a calcium- and receptor-independent mechanism.

Clenbuterol (10-100 microM), a beta 2-adrenergic agonist, potentiated basal (unstimulated) and electrical stimulation-evoked release of 3H-norepinephrine from cerebral cortical slices in a concentration-dependent manner. The beta-adrenergic antagonists propranolol and ICI 118,551 did not antagonize the facilitatory effect of clenbuterol on basal 3H-norepinephrine efflux. Selective down-regulation of beta 2-adrenergic receptors produced by chronic administration of clenbuterol also did not alter this effect of in vitro clenbuterol, despite marked reductions in the density of these receptors. These results suggest that the increase in basal efflux of 3H-norepinephrine observed with clenbuterol was not mediated by beta 2-adrenergic receptors. The facilitatory effect of clenbuterol on basal 3H-norepinephrine efflux was Ca(2+)-independent, which may indicate an amphetamine-like mechanism of action. The enhanced basal efflux of 3H-norepinephrine produced by clenbuterol was stereoselective; there was a four-fold increase in basal 3H-norepinephrine efflux with the (+)-isomer of clenbuterol compared with that induced by the (-)-isomer; this contrasts with the stereoselectivity of the isomers for interacting with beta 2-adrenergic receptors. The present results may explain some of the behavioral actions of clenbuterol, particularly those observed after long-term treatment, and may be relevant to the antidepressant actions of this compound.

Adrenergic beta-Antagonists↗