Modulation of positive inotropy and metabolic coronary dilatation by myocardial α-adrenoceptors

1985 ◽  
Vol 63 (12) ◽  
pp. 1513-1521 ◽  
Author(s):  
Bruce J. Youngson ◽  
Jaime Talesnik
Keyword(s):  
Calcium Chloride ◽  
Blood Supply ◽  
Sympathetic Stimulation ◽  
Inotropic Action ◽  
Ischaemic Damage ◽  
Rat Hearts ◽  
Coronary Vasodilatation ◽  
Dependent Inhibition ◽  
Adrenoceptor Agonists ◽  
Inotropic Responses

Cardiac hyperactivity and its consequent metabolically induced coronary vasodilatation (MCD) were studied in isolated, perfused, electrically paced rat hearts. The α-adrenoceptor agonists, phenylephrine and methoxamine, produced a concentration-dependent inhibition of the inotropic responses to noradrenaline, dobutamine, isoprenaline, tyramine, and glucagon, while relatively potentiating their MCD reactions. This inhibition was unrelated to the α-agonists' known inotropic action and was not affected by catecholamine depletion of the heart. Withdrawal of the α-agonists or administration of the α-adrenoceptor antagonists phentolamine, phenoxybenzamine, or prazosin returned the inotropic and MCD reactions to normal. Neither the MCD response to electrically induced tachycardia nor the inotropic reactions produced by calcium chloride were affected by α-adrenoceptor agonists or antagonists. Alone, α-adrenoceptor antagonists were shown to potentiate the inotropic responses to noradrenaline and isoprenaline while the MCD was relatively diminished. The responses to glucagon were unaltered by α-antagonists. We postulate that myocardial reactivity to sympathetic stimulation can be modulated through α-adrenoceptors by the inhibition of processes that mediate cardiostimulation at post-β-adrenoceptor sites, together with facilitation of those leading up to MCD. Accordingly, this modulation would act to prevent ischaemic damage to the heart by acting to limit the inotropic responses to increasing sympathetic stimulation while maximizing the blood supply to the myocardium.

scholarly journals Dissociation of Chronotropic and Inotropic Responses in the Rat Heart During Sympathetic Stimulation

1999 ◽  
Vol 63 (9) ◽  
pp. 710-717 ◽  
Author(s):  
Norio Onuki ◽  
Hisayuki Takahashi ◽  
Hitoshi Suzuki ◽  
Tomiyoshi Saito ◽  
Kazuhira Maehara ◽  
...  
Keyword(s):  
Rat Heart ◽  
Sympathetic Stimulation ◽  
Inotropic Responses

Purinergic Component in the Coronary Vasodilatation to Acetylcholine after Ischemia-Reperfusion in Perfused Rat Hearts

2014 ◽  
Vol 51 (4) ◽  
pp. 283-289 ◽  
Author(s):  
Ángel Luis García-Villalón ◽  
Miriam Granado ◽  
Luis Monge ◽  
Nuria Fernández ◽  
Gonzalo Carreño-Tarragona ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Rat Hearts ◽  
Coronary Vasodilatation ◽  
Perfused Rat Hearts

Beta 2-adrenoceptor agonists inhibit NANC neural bronchoconstrictor responses in vitro

1993 ◽  
Vol 74 (3) ◽  
pp. 1195-1199 ◽  
Author(s):  
G. M. Verleden ◽  
M. G. Belvisi ◽  
K. F. Rabe ◽  
M. Miura ◽  
P. J. Barnes
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Electrical Field Stimulation ◽  
Sensory Nerves ◽  
Inhibitory Effects ◽  
Exogenous Substance ◽  
Dependent Inhibition ◽  
Adrenoceptor Agonists ◽  
Beta 2

Nonadrenergic noncholinergic (NANC) contractile responses in guinea pig bronchi are due to the release of tachykinins from airway sensory nerves. The purpose of this study was to determine whether beta 2-receptor agonists modulate NANC contractions in guinea pig bronchi in vitro. Bronchial rings were suspended in organ baths for isometric measurement of tension, and comparable contractions were induced by electrical field stimulation (EFS; 40 V, 0.5 ms, 8 Hz for 20 s) or by exogenous substance P (3 microM). Aformoterol and salbutamol produced concentration-dependent inhibition of the NANC contraction, with aformoterol being ninefold more potent than salbutamol; approximate 50% inhibitory concentrations for aformoterol and salbutamol were 1.03 nM (n = 6) and 9.3 nM (n = 6), respectively. Aformoterol also inhibited the contraction induced by exogenous substance P but to a far lesser extent than its inhibition of EFS-induced responses. The inhibitory effects of formoterol (10 nM) on responses to EFS at 8 Hz were significantly prevented by propranolol (1 microM) and ICI 118551 (a beta 2-antagonist, 0.1 microM) but not by atenolol (a beta 1-antagonist, 1 microM) or phentolamine (10 microM). These experiments demonstrate that beta 2-agonists may modulate the release of tachykinins from airway sensory nerves by prejunctional receptors.

Heart rate as a determinant of the decay rate of the cardiac inotropic response to sympathetic nervous activity

1983 ◽  
Vol 61 (11) ◽  
pp. 1374-1381 ◽  
Author(s):  
Yukitaka Masuda ◽  
Matthew N. Levy
Keyword(s):  
Heart Rate ◽  
Sinus Rhythm ◽  
Nervous Activity ◽  
Ventricular Myocardium ◽  
Sympathetic Nervous Activity ◽  
Inotropic Response ◽  
Sympathetic Stimulation ◽  
Junctional Rhythm ◽  
Decay Times ◽  
Inotropic Responses

The cardiac responses to sympathetic nerve stimulation were measured in a series of open-chest, anesthetized dogs. In half the animals, the hearts were in a sinus rhythm; in the remaining animals, the hearts were in an atrioventricular (AV) junctional rhythm. Cocaine markedly prolonged the decay times of the chronotropic responses after cessation of sympathetic stimulation, regardless of the type of rhythm. The decay times of the inotropic responses were only slightly prolonged by cocaine in animals with a sinus rhythm, but the prolongations were pronounced in animals with an AV junctional rhythm. The lower basal heart rate appeared to be more responsible for the greater decay times of the inotropic responses in the animals with an AV junctional rhythm than in those with a sinus rhythm. In a second series of dogs, complete heart block was produced, cocaine was given, AND the hearts were paced at four different frequencies. The mean decay time of the inotropic response to sympathetic stimulation varied inversely AND substantially with the pacing frequency. The change in contraction frequency probably affects the rate of neurotransmitter dissipation from the ventricular myocardium, by altering either the coronary blood flow or the massaging action of the cardiac contractions.

scholarly journals The Antiarrhythmic Activity of Novel Pyrrolidin-2-one Derivative S-75 in Adrenaline-Induced Arrhythmia

2021 ◽  
Vol 14 (11) ◽  
pp. 1065
Author(s):  
Klaudia Lustyk ◽  
Kinga Sałaciak ◽  
Paula Zaręba ◽  
Agata Siwek ◽  
Jacek Sapa ◽  
...  
Keyword(s):  
Calcium Chloride ◽  
Adrenergic Receptors ◽  
Normal Sinus Rhythm ◽  
Heart Rhythm ◽  
Antiarrhythmic Activity ◽  
Significant Activity ◽  
Qtc Interval ◽  
Rat Hearts ◽  
Heart Rhythm Disorders ◽  
Isolated Rat

Arrhythmia is a quivering or irregular heartbeat that can often lead to blood clots, stroke, heart failure, and other heart-related complications. The limited efficacy and safety of antiarrhythmic drugs require the design of new compounds. Previous research indicated that pyrrolidin-2-one derivatives possess an affinity for α1-adrenergic receptors. The blockade of α1-adrenoceptor may play a role in restoring normal sinus rhythm; therefore, we aimed to verify the antiarrhythmic activity of novel pyrrolidin-2-one derivative S-75. In this study, we assessed the influence on sodium, calcium, potassium channels, and β1-adrenergic receptors to investigate the mechanism of action of S-75. Lack of affinity for β1-adrenoceptors and weak effects on ion channels decreased the role of these adrenoceptors and channels in the pharmacological activity of S-75. Next, we evaluated the influence of S-75 on normal ECG in rats and isolated rat hearts, and the tested derivative did not prolong the QTc interval, which may confirm the lack of the proarrhythmic potential. We tested antiarrhythmic activity in adrenaline-, aconitine- and calcium chloride-induced arrhythmia models in rats. The studied compound showed prophylactic antiarrhythmic activity in the adrenaline-induced arrhythmia, but no significant activity in the model of aconitine- or calcium chloride-induced arrhythmia. In addition, S-75 was not active in the model of post-reperfusion arrhythmias of the isolated rat hearts. Conversely, the compound showed therapeutic antiarrhythmic properties in adrenaline-induced arrhythmia, reducing post-arrhythmogen heart rhythm disorders, and decreasing animal mortality. Thus, we suggest that the blockade of α1-adrenoceptor might be beneficial in restoring normal heart rhythm in adrenaline-induced arrhythmia.

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.

Alpha 1-adrenoceptor-mediated phosphoinositide breakdown and inotropic responses in diabetic hearts

1991 ◽  
Vol 260 (2) ◽  
pp. H557-H562 ◽  
Author(s):  
H. Xiang ◽  
J. H. McNeill
Keyword(s):  
Positive Inotropic Effect ◽  
Binding Assay ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Protein Binding Assay ◽  
Rat Hearts ◽  
Induced Changes ◽  
Inotropic Responses

The mechanism(s) involved in diabetes-induced changes in the heart is still unclear, but one defect appears to occur in the alpha 1-adrenoceptor system. We evaluated the possibility that the changes in the inotropic responsiveness to alpha 1-adrenoceptor stimulation in streptozotocin-diabetic rat hearts may be linked to altered phosphoinositide turnover. Stimulation of alpha 1-adrenoceptor by norepinephrine (in the presence of propranolol) in right ventricles resulted in the formation of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] [measured with an Ins(1,4,5)P3 protein binding assay kit] in a time- and concentration-dependent manner in both control and diabetic rats. The increase in Ins(1,4,5)P3 preceded the increase in the norepinephrine-mediated positive inotropic effect. Diabetic hearts showed a greater maximum inotropic response to norepinephrine stimulation and also had higher Ins(1,4,5)P3 levels. These observations suggest that the changes in Ins(1,4,5)P3 levels may be implicated in the increased inotropic responsiveness to alpha 1-adrenoceptor stimulation in diabetic hearts. Ca2+ overload, induced by Ins(1,4,5)P3, could further be involved in the development of diabetic cardiomyopathy.

Enhanced chronotropic and inotropic responses of rat myocardium to cholinergic stimulus with aging

1992 ◽  
Vol 70 (12) ◽  
pp. 1618-1624 ◽  
Author(s):  
Na Su ◽  
Njanoor Narayanan
Keyword(s):  
Muscarinic Receptor ◽  
Heart Function ◽  
Specific Binding ◽  
Adrenergic Stimulation ◽  
Chronotropic Response ◽  
Related Difference ◽  
Age Related ◽  
Rat Hearts ◽  
Inotropic Responses ◽  
The Impact

The ability of the heart to respond to adrenergic stimulation diminishes with aging, and this may be one of the factors contributing to the age-associated decline in cardiac stress responsiveness. On the other hand, little is known about the impact of aging on the responsiveness of the heart to cholinergic stimulation. In this study, we determined the chronotropic and inotropic responses of the isolated, Langendorff-perfused hearts from adult (6–8 months) and aged (28–30 months) rats to cholinergic agonists so as to assess age-related alterations in postsynaptic cholinergic control of heart function. The results showed the following. (i) In isolated perfused spontaneously beating rat hearts, the negative chronotropic response to acetylcholine (10−9–10−5 M) was up to 4-fold greater in the aged compared with adult hearts; this age-related difference was less marked (2-fold) but not abolished in the presence of a maximally effective concentration (5 μM) of the cholinesterase inhibitor eserine. (ii) The cholinesterase-resistant agonist carbachol (10−9–2.5 × 10−6 M) elicited a 2- to 3-fold greater negative chronotropic response in the aged compared with adult hearts. (iii) In isolated perfused, electrically paced (4 Hz) rat hearts, carbachol (10−9–10−3 M) elicited a concentration-dependent negative inotropic response, which was 2-fold greater in the aged compared with adult heart at all carbachol concentrations, (iv) Acetylcholinesterase activities (micromoles per gram per hour) were 50–60% lower in the aged atria (83 ± 21) and ventricles (24 ± 6) than in adult atria (210 ± 20) and ventricles (47 ± 7). (v) No significant age-related difference was observed in the specific binding of (–)-[3H]quinuclidinyl benzilate to muscarinic receptor sites in atria or ventricles. These findings demonstrate a striking enhancement in the responses of the heart to cholinergic stimulus with aging, which can be attributed in part, but not solely to age-associated decline in cholinesterase activity. Age-associated alterations in muscarinic receptor linked events may also underlie the cholinergic hypersensitivity of the aging heart.Key words: aging, muscarinic receptor, cardiac performance in vitro, cholineresterase activity.

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