Adrenergic–cholinergic interactions in left atria. II. Comparison of the antagonism of inotropic responses to α- and β-adrenoceptor stimulation and BAY K 8644 by carbachol, D-600, and nifedipine

1987 ◽  
Vol 65 (10) ◽  
pp. 2059-2064 ◽  
Author(s):  
K. M. MacLeod
Keyword(s):  
Bay K 8644 ◽  
Muscarinic Agonist ◽  
Functional Interaction ◽  
Low Concentrations ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists ◽  
Β Blocker ◽  
Β Receptor ◽  
The Right ◽  
Inotropic Responses

The muscarinic agonist carbachol has previously been shown to reverse positive inotropic responses of rabbit left atrial strips to equiactive doses of the β-adrenoceptor agonist isoproterenol and to the α-adrenoceptor agonist phenylephrine. Responses to phenylephrine were measured in the presence of the β-blocker timolol. However, carbachol was not able to reverse the increase in tension produced by elevating the extracellular Ca2+ concentration. To gain more information about the nature of the functional interaction of carbachol with α- and β-receptor stimulants in left atria, the interaction of carbachol with these agonists, as well as with elevated Ca2+ and the Ca2+ activator compound BAY K 8644, was compared with that of the Ca2+ antagonists D-600 and nifedipine. The results demonstrate that the Ca2+ antagonists exhibit a selectivity similar to that of carbachol, in that responses to both isoproterenol and phenylephrine plus timolol were blocked by low concentrations of D-600 and nifedipine, which had no effect on positive inotropic responses to elevated Ca2+. Higher concentrations of these antagonists shifted the Ca2+ dose–response curve to the right. In addition, although phenylephrine and BAY K 8644 increased tension to a similar extent, responses to phenylephrine were more sensitive than responses to BAY K 8644 to inhibition by both carbachol and D-600. These similarities between the effects of low concentrations of D-600 and nifedipine and those of carbachol are consistent with the hypothesis that carbachol antagonizes responses to α- and β-receptor stimulation in left atria primarily by blocking increases in Ca2+ influx produced by these agonists. In addition, the observation that responses of left atria to α- and β-adrenoceptor agonists are blocked more readily than responses to elevated Ca2+ and those to BAY K 8644 by both carbachol and the Ca2+ antagonists may be indicative of differences in the way agonists on one hand, and elevated Ca2+ and BAY K 8644 on the other, increase Ca2+ influx into myocardial cells.

Adrenergic–cholinergic interactions in left atria: Interaction of carbachol with alpha- and beta-adrenoceptor agonists

1986 ◽  
Vol 64 (5) ◽  
pp. 597-601 ◽  
Author(s):  
K. M. MacLeod
Keyword(s):  
Left Atrial ◽  
Muscarinic Agonist ◽  
Muscarinic Agonists ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Agonists ◽  
Β Receptor ◽  
Inotropic Responses ◽  
Beta Adrenoceptor Agonists ◽  
Camp Levels ◽  
Dose Dependent

The purpose of the present investigation was to determine the nature of the functional interaction of muscarinic agonists with cAMP-generating and cAMP-independent agonists in left atria. Negative inotropic responses of rabbit isolated left atrial strips to the muscarinic agonist, carbachol were measured in the absence and presence of equi-active inotropic doses of the β-adrenoceptor stimulant isoproterenol (Iso), the mixed α- and β-adrenoceptor stimulant phenylephrine (PE) plus 1 μM timolol to block the β-receptor mediated component of its response, and elevated extracellular Ca2+. Carbachol produced dose-dependent negative inotropic responses in left atrial strips, which were much greater than control in the presence of either Iso, or PE plus timolol. However, carbachol responses were of a similar magnitude to the control in the presence of elevated extracellular Ca2+. In the presence of timolol, PE had no significant effect on cAMP levels in left atrial strips, and inotropic responses to carbachol alone and in combination with PE plus timolol were accompanied by significant increases in cGMP levels but no change in cAMP levels. Carbachol attenuated Iso-induced increases in cAMP levels, but decreases in left atrial tension were proportionally greater than the decreases in cAMP levels produced by carbachol in the presence of Iso. These results suggest that the antiadrenergic effects of muscarinic receptor stimulation may occur by a different mechanism in left atria than has been previously reported in ventricular muscle. While the nature of this mechanism is unknown, it may involve antagonism by muscarinic agents of both α-and β-adrenoceptor mediated increases in Ca2+ influx.

Changes in Astroglial Cell Volume after Exposure to HgCl2 or CH3HgCl

1992 ◽  
Vol 20 (2) ◽  
pp. 246-250
Author(s):  
Lars Rönnbäck ◽  
Elisabeth Hansson
Keyword(s):  
Glucose Uptake ◽  
Cell Volume ◽  
Receptor Agonist ◽  
Primary Cultures ◽  
Control Cell ◽  
Astroglial Cell ◽  
Receptor Stimulation ◽  
Adrenoceptor Agonists ◽  
Β Receptor ◽  
Induced Changes

Cell volume was determined by measuring [14C]-3- O-methyl glucose uptake in astroglial-enriched primary cultures. Control cell volume was 3.20μl/mg protein. After incubation in 10 5M HgCl2 for 60 minutes, there was a 71% increase in cell volume. This increase was partially inhibited in the presence of the α1 receptor agonist, phenylephrine, or by the α2 receptor agonist clonidine, and was completely reversible by their respective antagonists, prazosine and yohimbine. The β receptor agonist, isoproterenol, which in itself increased cell volume, and 5-hydroxytryptamine (5HT) did not affect the HgCl2-induced changes in cell volume. 10 5M CH3HgCl increased cell volume by 26% after 30 minutes of incubation. This increase was not significantly influenced by adrenoceptor agonists or 5HT. It therefore seems that mercurial-induced changes in cell volume can be regulated by astroglial receptor stimulation.

Effects of α-adrenoceptor agonists and antagonists on thyroid hormone secretion

1985 ◽  
Vol 108 (2) ◽  
pp. 184-191 ◽  
Author(s):  
Bo Ahrén
Keyword(s):  
Thyroid Hormone ◽  
Dose Level ◽  
Hormone Secretion ◽  
High Dose ◽  
Inhibitory Effects ◽  
High Dose Level ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists

Abstract. The effects of various α-adrenoceptor agonists and antagonists on blood radioiodine levels were studied in mice pre-treated with 125I and thyroxine. The non-selective α-adrenoceptor agonist noradrenaline and the selective α1-adrenoceptor agonist phenylephrine both enhanced blood radioiodine levels. Noradrenaline was more potent than phenylephrine. Contrary, the selective α2-adrenoceptor agonist clonidine depressed basal levels of blood radioiodine. The non-selective α-adrenoceptor antagonist phentolamine and the selective α1-adrenoceptor antagonist prazosin both inhibited the noradrenaline-induced elevation of radioiodine levels, whereas the α2-adrenoceptor antagonist yohimbine had no such effect, except at a high dose level. All three α-adrenoceptor agonists, noradrenaline, phenylephrine and clonidine, inhibited the radioiodine response to TSH. In addition, TSH-induced increase in radioiodine levels was inhibited by prazosin, whereas yohimbine had no effect. Phentolamine inhibited the radioiodine response to TSH when given 2 h prior to TSH, whereas when given 15 min prior to TSH the response to TSH was potentiated by Phentolamine. It is concluded, that under in vivo conditions in the mouse, α1-adrenoceptor activation stimulates basal thyroid hormone secretion and inhibits TSH-induced thyroid hormone secretion. Further, α2-adrenoceptor activation inhibits basal thyroid hormone secretion. In addition, TSH-induced thyroid hormone secretion is inhibited by α1-adrenoceptor antagonism. Thus, α-adrenoceptors induce both stimulatory and inhibitory effects of thyroid function.

Controlled β-Receptor Blockade with Flestolol: A Novel Ultrashort-Acting β-Blocker

1987 ◽  
Vol 9 (1) ◽  
pp. 72-78 ◽  
Author(s):  
Vishnubhakta S. Murthy ◽  
Tsae-Fung Hwang ◽  
Leon B. Rosen ◽  
Richard J. Gorczynski
Keyword(s):  
Receptor Blockade ◽  
Β Blocker ◽  
Β Receptor

Positive inotropic effects of low concentrations of leukotrienes C4 and D4 in rat heart

1990 ◽  
Vol 259 (4) ◽  
pp. H1239-H1246 ◽  
Author(s):  
M. Karmazyn ◽  
M. P. Moffat
Keyword(s):  
Calcium Channel ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Bay K 8644 ◽  
Inotropic Effect ◽  
Receptor Interaction ◽  
Inotropic Effects ◽  
Coronary Pressure ◽  
Low Concentrations ◽  
Rat Hearts

We examined the effects of leukotrienes (LT) B4, C4, D4, and E4 (0.010-2.5 ng/ml) on contractile and coronary function in isolated rat hearts. Concentration-dependent effects were examined either by the cumulative addition of LTs or by addition of specific concentrations to individual preparations. Neither LTB4 nor LTE4 produced myocardial or coronary effects at any concentration, irrespective of addition protocol. At 0.010 ng/ml, both LTC4 and LTD4 produced an increase in force that was associated with a 30% elevation in coronary pressure. Further cumulative addition of either leukotriene resulted in a negative inotropic effect and a further increase in coronary pressure. In contrast, following single additions of LTC4 or LTD4 (0.01-0.50 ng/ml) a positive inotropic effect and an increased coronary pressure were observed. LTC4 or LTD4 at 0.5 ng/ml produced a negative inotropic effect in hearts pretreated with 0.01 ng/ml of LTD4 or LTC4, respectively. Reversal of this addition protocol resulted in a negative inotropic effect of either 0.01 ng/ml LTD4 or LTC4. Verapamil and nifedipine significantly attenuated the positive inotropic and coronary constricting effect of 0.5 ng/ml LTC4 and LTD4. The addition of either LT following BAY K 8644 resulted in a negative inotropic effect, in contrast to the positive inotropic influence seen with leukotriene alone. Our results demonstrate a positive inotropic effect of low concentrations of LTC4 and LTD4 concomitant with coronary artery constriction, a phenomenon determined by leukotriene addition protocols and suggestive of LTC4/LTD4 receptor interaction. The effects of calcium channel antagonists and BAY K 8644 on the inotropic response suggest a leukotriene-mediated activation of the calcium channel resulting in increased intracellular calcium concentrations.

Differential pre- and postsynaptic effects of desipramine on cardiac sympathetic nerve terminals in RHF

2002 ◽  
Vol 283 (5) ◽  
pp. H1863-H1872 ◽  
Author(s):  
Chang-Seng Liang ◽  
Yoshihiro Himura ◽  
Michihiro Kashiki ◽  
Suzanne Y. Stevens
Keyword(s):  
Sympathetic Nerve ◽  
Glyoxylic Acid ◽  
Nerve Endings ◽  
Immunocytochemical Staining ◽  
Receptor Density ◽  
Cardiac Sympathetic Nerve ◽  
Uptake Inhibition ◽  
Uptake Activity ◽  
Β Receptor ◽  
Inotropic Responses

Right heart failure (RHF) is characterized by chamber-specific reductions of myocardial norepinephrine (NE) reuptake, β-receptor density, and profiles of cardiac sympathetic nerve ending neurotransmitters. To study the functional linkage between NE uptake and the pre- and postsynaptic changes, we administered desipramine (225 mg/day), a NE uptake inhibitor, to dogs with RHF produced by tricuspid avulsion and progressive pulmonary constriction or sham-operated dogs for 6 wk. Animals receiving no desipramine were studied as controls. We measured myocardial NE uptake activity using [3H]NE, β-receptor density by [125I]iodocyanopindolol, inotropic responses to dobutamine, and noradrenergic terminal neurotransmitter profiles by glyoxylic acid-induced histofluorescence for catecholamines, and immunocytochemical staining for tyrosine hydroxylase and neuropeptide Y. Desipramine decreased myocardial NE uptake activity and had no effect on the resting hemodynamics in both RHF and sham animals but decreased myocardial β-adrenoceptor density and β-adrenergic inotropic responses in both ventricles of the RHF animals. However, desipramine treatment prevented the reduction of sympathetic neurotransmitter profiles in the failing heart. Our results indicate that NE uptake inhibition facilitates the reduction of myocardial β-adrenoceptor density and β-adrenergic subsensitivity in RHF, probably by increasing interstitial NE concentrations, but protects the cardiac noradrenergic nerve endings from damage, probably via blockade of NE-derived neurotoxic metabolites into the nerve endings.

Atrioventricular responses of canine heart following chronic unilateral vagotomy

1987 ◽  
Vol 253 (2) ◽  
pp. H394-H401 ◽  
Author(s):  
D. V. Priola ◽  
C. Anagnostelis ◽  
C. Sanchez-Wilson ◽  
T. M. Blomquist
Keyword(s):  
Frequency Response ◽  
Control Mechanisms ◽  
Canine Heart ◽  
Response Curves ◽  
Group Iii ◽  
Group I ◽  
Group Ii ◽  
The Right ◽  
Inotropic Responses ◽  
Intrinsic Cardiac Nerves

The intrinsic cardiac nerves (ICN) have been shown to develop supersensitivity to nicotine (NIC) following complete extrinsic cardiac denervation. The present experiments were performed to delineate the pattern of ICN distribution in the heart by examining the pattern of NIC supersensitivity after unilateral vagotomy (VGX). Thirty-eight dogs were placed on cardiopulmonary bypass and inotropy evaluated by means of isovolumic pressures from fluid-filled balloons placed in the atria and ventricles. The animals were divided into three groups: group I, sham-operated controls; group II, animals studied 1–2 wk after VGX; and group III, animals studied 8–12 wk after VGX. Chronotropic and inotropic responses were evaluated in terms of NIC and acetylcholine (ACh) dose-response curves as well as frequency-response curves to stimulation of the intact vagus nerve (0.5–30 Hz). No change in NIC sensitivity was observed in group II, and vagal frequency-response curves were identical to group I. In group III dogs, both the right atrium and right ventricle showed significant increases in NIC sensitivity after left vagotomy. All group III animals showed right-shifted frequency-response curves. We conclude that nicotinic supersensitivity of the ICN and inotropic unresponsiveness to vagal stimulation occur but are slow in developing (70–130 days); and preganglionic sprouting does not appear to play a functional role in the adjustment of cardiac control mechanisms to unilateral vagotomy.

Characterization of the effects of AHN 086, an irreversible ligand of "peripheral" benzodiazepine receptors, on contraction in guinea-pig atria and ileal longitudinal smooth muscle

1989 ◽  
Vol 67 (2) ◽  
pp. 126-134 ◽  
Author(s):  
G. T. Bolger ◽  
A. H. Newman ◽  
K. C. Rice ◽  
H. W. M. Lueddens ◽  
A. S. Basile ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Calcium Channels ◽  
Benzodiazepine Receptors ◽  
Significant Inhibition ◽  
Bay K 8644 ◽  
Longitudinal Smooth Muscle ◽  
Peripheral Benzodiazepine Receptors ◽  
Inotropic Responses ◽  
Guinea Pig Atria

The effects of AHN 086 and its reversibly acting structural analogue Ro 5-4864 were studied in the spontaneously beating guinea-pig atria and field-stimulated guinea-pig ileal longitudinal smooth muscle in the presence and absence of dihydropyridine calcium channel modulators. The treatment of guinea-pig atria with AHN 086 followed by extensive washing did not alter contraction. However, AHN 086 (0.5 μM) potentiated (88%) the positive inotropic responses by BAY K 8644, an effect that was not reversed by extensive washing of the tissue. Higher concentrations of AHN 086 (> 2 μM) irreversibly inhibited the intropic, but not the chronotropic responses to BAY K 8644, nifedipine, and isoproterenol. Ro 5-4864 (10 μM) produced a reversible enhancement of the inotropic responses and block of the chronotropic responses to BAY K 8644. In guinea-pig ileal longitudinal smooth muscle, both AHN 086 and Ro 5-4864 reversibly inhibited field-stimulated contractions. Neither Ro 5-4864 nor AHN 086 affected the ability of nifedipine to inhibit field-stimulated contractions of ileal longitudinal smooth muscle. Treatment of intact atria with 5 μM AHN 086 followed by extensive washing resulted in a significant inhibition (30–50%) of [3H]Ro 5-4864 binding to peripheral benzodiazepine receptors and of [3H]nitrendipine binding to voltage-operated calcium channels, but did not affect [3H]dihydroalprenolol binding to β-adrenergic receptors on atrial membranes. The same treatment applied to intact ileal longitudinal smooth muscle affected neither [3H] (−)-quinuclidinyl benzilate binding to muscarine receptors nor [3H]nitrendipine binding, but did result in a significant inhibition (30–50%) of [3H]Ro 5-4864 binding to ileal longitudinal smooth muscle membranes. The pharmacology of AHN 086 suggests that there is a different relationship between peripheral benzodiazepine receptors and voltage-operated calcium channels in guinea-pig atria and ileal longitudinal smooth muscle.Key words: calcium channels, peripheral benzodiazepine receptors, dihydropyridines, benzodiazepines, dihydropyridine binding sites.

Copper inhibits pressor responses to noradrenaline but not potassium. Interactions with prostaglandins E1, E2, and I2 and penicillamine

1979 ◽  
Vol 57 (1) ◽  
pp. 35-40 ◽  
Author(s):  
S. C. Cunnane ◽  
H. Zinner ◽  
D. F. Horrobin ◽  
M. S. Manku ◽  
R. O. Morgan ◽  
...  
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Biological Action ◽  
Dose Response Curve ◽  
Low Concentrations ◽  
Pressor Responses ◽  
The Right ◽  
Copper Effect

Low concentrations of copper inhibited responses to norepinephrine and angiotensin (IC50 3 × 10−6 M) but not to potassium in rat mesenteric vascular preparations perfused either with buffer or indomethacin and prostaglandin (PGE2). The dose–response curve was not shifted by indomethacin, imidazole, or PGE2 but was moved to the right by 2.8 × 10−11 M PGE1 and to the left by 2.8 × 10−7 M PGE1. These effects of copper are similar to the effects of PGI2 in the preparation. Copper moved the PGI2 dose–response curve against noradrenaline in parallel to the left, suggesting that the two were interacting at some point. Penicillamine, which may stimulate PGE1 synthesis, had PGE1-like interactions with the copper effect, suggesting that its value in Wilson's disease may be partly due to antagonism of the biological action of copper as well as to its copper-chelating properties.

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