Histochemical and Chemical Studies of the Localization of Adrenergic and Cholinergic Nerves in Normal and Denervated Cat Hearts

Jacobowitz, David M.; Cooper, Theodore; Barner, Hendrick B.

doi:10.1161/01.res.20.3.289

Cited by 156 publications

(43 citation statements)

References 12 publications

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“…Considerable anatomical evidence exists for the presence of cholinergic receptors in the ventricles (11)(12)(13)(14)(15)(16)(17). Furthermore, acetylcholinesterase activity has…”

Section: Discussionmentioning

confidence: 99%

Effects of Acetylcholine on Automaticity and Conduction in the Proximal Portion of the His-Purkinje Specialized Conduction System of the Dog

Bailey

Greenspan

Elizari

et al. 1972

Circulation Research

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Conventional intracellular recordings from the bundle of His and right bundle branch of the canine heart demonstrated that the slope of diastolic depolarization is markedly depressed by superfusion with relatively small concentrations (4-8 jug/ml) of acetylcholine. As the cells become less automatic, take-off potential increases, rise time of phase 0 is reduced, action potential amplitude increases, and conduction proceeds more rapidly.KEY WORDS right bundle branch determinants of conductivity spontaneous phase 4 depolarization transmembrane action potential innervation of the heart • Early investigations indicated that cells of the specialized conduction system below the atrioventricular (AV) junction are unaffected by small concentrations of acetylcholine (1). Specifically, the slope of spontaneous phase 4 depolarization from cells of the bundle of His, bundle branches, and peripheral Purkinje fibers is reported to be essentially unchanged by the infusion of acetylcholine. A method of exposing the entire proximal portion of the specialized AV conduction system of the canine heart in vitro was devised by one of the authors (M.V.E.), and the regular observation of automaticity afforded the opportunity to reexamine certain aspects of this property.From the Krannert Institute of Cardiology, Marion County General Hospital, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202.This work was supported in part by U. S. Public Health Service Grants HE-6308, HTS-5363, and HE-5749 from the National Heart Institute and by the Herman C. Krannert Fund, the Indiana Heart Association, and the AMA Committee for Research on Tobacco and Health. Drs. Bailey, Elizari, and Anderson are U. S. Public Health Service Trainees in Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202.Received July 30, 1971. Accepted for publication November 29, 1971. The purpose of this paper is to report our studies of the effects of small doses of acetylcholine on spontaneity and conduction within the proximal portion of the HisPurkinje conduction pathways. MethodsAdult mongrel dogs of either sex weighing 15-20 kg were anesthetized with sodium pentobarbital (30 mg/kg, i.v.) and intubated; respiration was controlled with a Harvard respirometer. The hearts were excised rapidly through a right thoracotomy, and the portion of the septum containing the AV junction, the bundle of His, and both bundle branches was removed, placed in a Lucite muscle chamber, and superfused with oxygenated Tyrode's solution maintained at a temperature of 31 ± 0.2°C. Then the entire bundle of His was exposed from the nodal His (NH) region of the AV junction to the origins of both bundle branches. Portions of the proximal part of the specialized AV conduction system were isolated, when appropriate, by transection. The tissue was then allowed to stabilize for several hours until muscular contraction ceased and to minimize changes in diastolic depolarization as a function of time and in...

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“…Considerable anatomical evidence exists for the presence of cholinergic receptors in the ventricles (11)(12)(13)(14)(15)(16)(17). Furthermore, acetylcholinesterase activity has…”

Section: Discussionmentioning

confidence: 99%

Effects of Acetylcholine on Automaticity and Conduction in the Proximal Portion of the His-Purkinje Specialized Conduction System of the Dog

Bailey

Greenspan

Elizari

et al. 1972

Circulation Research

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“…An earlier study is germane to this point: we employed the same degree of pulmonary artery banding in the cat as that used here, but for 60 wk before study (25), an interval greater than that reported to be required for the reinnervation of the hearts of cats (44) or dogs (45) after deliberate surgical cardiac denervation. The heart rate of these cats (25) during anesthesia with 25 mg/kg of ketamine, a phencyclidine derivative with centrally mediated sympathomimetic activity (46), was 181±7 beats/min; for normal control cats in our laboratory after the same anesthesia a similar value of 186±9 beats/min was obtained, but in the identically anesthetized cats with epicardial denervation in the present study, this value was significantly lower at 152±5 beats/min, a value not greatly different from that of 110-140 beats/min which we see in awake, unrestrained cats.…”

Section: Adrenergic Interventionsmentioning

confidence: 99%

Hemodynamic versus adrenergic control of cat right ventricular hypertrophy.

Th¹,

Kent²,

Uboh³

et al. 1985

J. Clin. Invest.

137

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The purpose of this study was to determine whether cardiac hypertrophy in response to hemodynamic overloading is a primary result of the increased load or is instead a secondary result of such other factors as concurrent sympathetic activation. To make this distinction, four experiments were done; the major experimental result, cardiac hypertrophy, was assessed in terms of ventricular mass and cardiocyte cross-sectional area. In the first experiment, the cat right ventricle was loaded differentially by pressure overloading the ventricle, while unloading a constituent papillary muscle; this model was used to ask whether any endogenous or exogenous substance caused uniform hypertrophy, or whether locally appropriate load responses caused ventricular hypertrophy with papillary muscle atrophy. The latter result obtained, both when each aspect of differential loading was simultaneous and when a previously hypertrophied papillary muscle was unloaded in a pressure overloaded right ventricle. In the second experiment, epicardial denervation and then pressure overloading was used to assess the role of local neurogenic catecholamines in the genesis of hypertrophy. The degree of hypertrophy caused by these procedures was the same as that caused by pressure overloading alone. In the third and fourth experiments, fi-adrenoceptor or a-adrenoceptor blockade was produced before and maintained during pressure overloading. The hypertrophic response did not differ in either case from that caused by pressure overloading without adrenoceptor blockade. These experiments demonstrate the following: first, cardiac hypertrophy is a local response to increased load, so that any factor serving as a mediator of this response must be either locally generated or selectively active only in those cardiocytes in which stress and/or strain are increased; second, catecholamines are not that mediator, in that adrenergic activation is neither necessary for nor importantly modifies the cardiac hypertrophic response to an increased hemodynamic load.

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“…• Histological studies done since the early 1960s have documented the presence of cholinergic innervation in the ventricular myocardium (1,2). In addition, a number of physiological experiments have demonstrated that stimulation of vagal nerves or administration of cholinergic drugs can depress, although often minimally, the contractile state of the ventricle (3-7).…”

mentioning

confidence: 99%

Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium.

Watanabe¹,

Besch²

1975

Circulation Research

229

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The purpose of this study was to examine the mechanisms underlying adrenergiccholinergic antagonism in ventricular myocardium. Myocardial contractility, cyclic adenosine monophosphate (AMP) levels, and cyclic guanosine monophosphate (GMP) levels were measured in isolated guinea pig ventricles after treatment with various inotropic agents given alone and simultaneously with acetylcholine. Acetylcholine alone markedly elevated cyclic GMP levels but did not substantially change myocardial contractility. However, the same concentration of acetylcholine significantly attenuated the inotropic effect of isoproterenol and histamine, two drugs that may act by increasing myocardial levels of cyclic AMP. The decrease in the inotropic response to isoproterenol did not appear to be due to a decrease in the generation of cyclic AMP, because cyclic AMP levels were similar in hearts receiving isoproterenol alone and those receiving isoproterenol with acetylcholine. Dibutyryl cyclic GMP also antagonized the inotropic action of isoproterenol. Acetylcholine did not alter the inotropic effects of ouabain, an agent that increases myocardial contractility without changing cyclic AMP levels. These results suggest that cyclic GMP mediates the antiadrenergic effects of acetylcholine by specifically antagonizing the inotropic actions of cyclic AMP.• Histological studies done since the early 1960s have documented the presence of cholinergic innervation in the ventricular myocardium (1, 2). In addition, a number of physiological experiments have demonstrated that stimulation of vagal nerves or administration of cholinergic drugs can depress, although often minimally, the contractile state of the ventricle (3-7). The ventricular depressant effect of the cholinergic system appears to be enhanced in the presence of adrenergic stimulation (8-13). This complex interaction between adrenergic and cholinergic effects on the heart, in which the cholinergic depressant action is magnified during sympathetic stimulation, has been termed accentuated antagonism by Levy (14).Several studies, all done with broken cell preparations or tissue slices, have also shown that cholinergic drugs can attenuate catecholamineinduced increases in cyclic adenosine monophosphate (AMP) levels in cardiac tissues (15,16 attenuation of the amount of cyclic AMP generated has logically been proposed as the mechanism, at the subcellular level, for the antagonism between the adrenergic and the cholinergic systems. With the recent demonstration that the level of cyclic guanosine monophosphate (GMP) in the myocardium is increased after cholinergic stimulation (16,17), it became of interest to investigate whether the interaction of the adrenergic and cholinergic systems at the subcellular level of the heart is occurring between cyclic AMP and cyclic GMP. The series of experiments reported in this paper was performed with the objective of attempting to correlate the contractile state of intact ventricular muscle with induced changes in cyclic nucleotide (cyclic AMP and cycl...

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Histochemical and Chemical Studies of the Localization of Adrenergic and Cholinergic Nerves in Normal and Denervated Cat Hearts

Cited by 156 publications

References 12 publications

Effects of Acetylcholine on Automaticity and Conduction in the Proximal Portion of the His-Purkinje Specialized Conduction System of the Dog

Effects of Acetylcholine on Automaticity and Conduction in the Proximal Portion of the His-Purkinje Specialized Conduction System of the Dog

Hemodynamic versus adrenergic control of cat right ventricular hypertrophy.

Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium.

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