Effect of sympathectomy on inotropic responsiveness to α-adrenoceptor stimulation in developing mouse myocardia

1995 ◽  
Vol 73 (9) ◽  
pp. 1285-1288 ◽  
Author(s):  
Hikaru Tanaka ◽  
Tomoyuki Matsuda ◽  
Mika Adachi ◽  
Koki Shigenobu
Keyword(s):  
Sympathetic Innervation ◽  
Ventricular Myocardium ◽  
Contractile Force ◽  
Inotropic Response ◽  
Maximum Decrease ◽  
6 Hydroxydopamine ◽  
Inotropic Responses

Effects of postnatal sympathectomy on inotropic responsiveness to α-adrenoceptor stimulation were examined in mouse myocardia to determine whether the developmental conversion of α-adrenoceptor-mediated inotropic responses from positive to negative is triggered by sympathetic innervation. Sympathectomy was performed chemically by consecutively administering 6-hydroxydopamine for 14 days after birth and confirmed by the absence of inotropic responses to tyramine. In newborn myocardia, phenylephrine, in the presence of propranolol, produced concentration-dependent positive inotropic responses. Three weeks after birth, phenylephrine, in the presence of propranolol, produced concentration-dependent negative inotropic responses, both in control and in sympathectomized myocardia; no difference was observed between the two groups of mice in the maximum decrease in contractile force produced by phenylephrine. The sensitivity (pD2 value) to phenylephrine was significantly higher in sympathectomized myocardia. In conclusion, sympathetic innervation of the mouse ventricular myocardium is not required for the developmental conversion of the α-adrenoceptor-mediated inotropic response from positive to negative.Key words: inotropism, α-adrenoceptor, supersensitivity, sympathetic innervation, development.

Ontogeny of positive inotropic responses to sympathomimetic agents and of myocardial adrenoceptors in rats

1994 ◽  
Vol 72 (4) ◽  
pp. 361-367 ◽  
Author(s):  
Arjumand Inayatulla ◽  
Ding-You Li ◽  
Sylvain Chemtob ◽  
Daya R. Varma
Keyword(s):  
Contractile Force ◽  
Inotropic Response ◽  
Chemical Sympathectomy ◽  
Adult Rats ◽  
Maximal Increase ◽  
Inotropic Effects ◽  
Mediated Effects ◽  
Adrenoceptor Agonist ◽  
6 Hydroxydopamine ◽  
Inotropic Responses

Positive inotropic efficacies (maximal increase in contractile force) and potencies of the α-adrenoceptor agonist methoxamine and β-adrenoceptor agonist isoprenaline were determined on electrically driven (1 Hz) ventricular strips from rats aged 0.5, 1, 2, 3, 6, and 10 (adult) weeks. The inotropic response to methoxamine significantly decreased after 2 weeks of age. The inotropic potency of isoprenaline was slightly but significantly lower at all ages than at 0.5 weeks of age. Up to 2 weeks of age, the maximal inotropic effect of methoxamine was comparable with that of isoprenaline, thereafter it was but markedly less. Phenylephrine behaved like methoxamine, and noradrenaline like isoprenaline. The effect of methoxamine was antagonized by prazosin but not by propranolol; the reverse was true for isoprenaline. Injections at birth of triiodothyronine and dexamethasone exerted minimal effects on the inotropic responses to methoxamine and isoprenaline. Chemical sympathectomy with 6-hydroxydopamine caused supersensitivity to the inotropic effects of isoprenaline but produced subsensitivity to responses to methoxamine at 1 week; effects of methoxamine at 3 and 6 weeks of age were not altered by sympathectomy. No significant differences in α1 or β1-adrenoceptor densities or affinities in ventricular membranes from 7-day-old and adult rats were found. It is concluded that the positive inotropic responses to sympathomimetic amines decline with age, the decline is most marked in the case of α1-adrenoreceptor-mediated effects, and these changes do not appear to be due to a decrease in the number or affinity of α1- and β1-adrenoceptors.Key words: myocardial adrenocepters, methoxamine, isoprenaline, phenylephrine, noradrenaline, ontogeny, inotropic responses.

scholarly journals Heart failure switches the RV α1-adrenergic inotropic response from negative to positive

2010 ◽  
Vol 298 (3) ◽  
pp. H913-H920 ◽  
Author(s):  
Guan-Ying Wang ◽  
Che-Chung Yeh ◽  
Brian C. Jensen ◽  
Michael J. Mann ◽  
Paul C. Simpson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Problem ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Coronary Artery Ligation ◽  
Inotropic Response ◽  
Artery Ligation ◽  
Protein Levels ◽  
Inotropic Responses

Right ventricular (RV) failure is a serious common clinical problem that is poorly understood. Therefore, for failing and nonfailing hearts, we examined the distinctive inotropic responses induced in the RV myocardium after the stimulation of α1-adrenergic receptors (ARs). In RV trabeculae from nonfailing mouse hearts, α1-ARs induced a negative inotropic response, consistent with our previous study. In marked contrast, in RV trabeculae from failing hearts, 12 wk after coronary artery ligation, α1-ARs induced a positive inotropic response. Mechanistically, experiments with skinned trabeculae showed that α1-ARs decreased myofilament Ca2+ sensitivity in the nonfailing RV myocardium, whereas α1-ARs increased Ca2+ sensitivity in heart failure. This suggests that a switch in the Ca2+ sensitivity response to α1-AR stimulation explained the switch in the RV α1-AR inotropic response in heart failure. Myosin light chain kinase (MLCK) can increase myofilament Ca2+ sensitivity, and the smooth muscle isoform (smMLCK), which is also present in cardiomyocytes, was more abundant in the RV myocardium from failing versus nonfailing hearts. Moreover, the MLCK inhibitor ML-9 prevented the switch of the RV myocardium to a positive α1-AR inotropic response in heart failure. In the left ventricular myocardium, in contrast, α1-AR inotropic responses were not different in failing versus nonfailing hearts, and smMLCK abundance was not increased in heart failure. In relation to human disease, we found that smMLCK mRNA and protein levels were increased in RVs from failing human hearts. We conclude that the RV inotropic response to α1-ARs is switched from negative to positive in heart failure, through a pathway involving increased myofilament Ca2+ sensitivity. Since α1-AR agonist catecholamines are elevated in heart failure, increased α1-AR inotropic responses in the RV myocardium may be adaptive in heart failure by helping the failing RV respond to increased pulmonary pressures.

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 ALPHA(1)-ADRENOCEPTORS ACTIVATION DECREASES MYOCARDIAL CONTRACTILITY IN NEWBORN RATS

2020 ◽  
Vol 8 (Spl-2-AABAS) ◽  
pp. S322-S326
Author(s):  
Insaf Ilkhamovich Khabibrakhmanov ◽  
◽  
Anna Mihailovna Kuptsova ◽  
Nafisa Ilgizovna Ziyatdinova ◽  
Nur Mansur ◽  
...  
Keyword(s):  
Adrenergic Receptors ◽  
Myocardial Contractility ◽  
Contractile Function ◽  
Ventricular Myocardium ◽  
Contractile Force ◽  
Fine Tuning ◽  
Newborn Rats ◽  
Newborn Rat ◽  
Rat Pups ◽  
Inotropic Responses

Alpha(1)-adrenergic receptors (α1-AR) are found in cardiomyocytes, endothelial cells, and smooth muscle cells of humans and animals. Despite the fact that α1-AR make up 10% of the total number of adrenergic receptors, these receptors also involved in the regulation of inotropic and chronotropic functions of the heart. According to some scientists, the effects of α1-AR activation are not required for the basal contractile function of the heart while other group of researchers believe that α1-AR can be considered as cardioprotective targets; in particular, it is postulated that the α1A-subtype of adrenergic receptors can provide significant inotropic support in cardiac pathologies. This study was carried out on 6-7-day-old outbred newborn rat pups to evaluate the effect of alpha(1)-adrenoceptors activation on the myocardial contractility in newborn rats. For this, Alpha1-adrenergic receptors were stimulated by the pharmacological drug methoxamine at concentrations of 10-9-10-6 mol and the reaction of the contractile force of the strips of myocardium ventricles and heart atria in response to the agonist was investigated. Results of study revealed that stimulation of alpha1-adrenergic receptors, regardless of the methoxamine concentration, led to a negative inotropic reaction of the myocardium of atria and ventricles of newborn rat pups. This study showed unidirectional inotropic responses on rat atrial and ventricular myocardium in response to α1-adrenergic receptors stimulation. Methoxamine smoothly reduces the contractile force of the strips of myocardium atria and ventricles. At the same time, the concentration dependence on the inotropic reaction of the myocardium was observed. Results of study suggested that probably α1-adrenergic receptors along with the main regulators β-adrenergic receptors carry out fine tuning of the heart activity.

Abstract 17185: Sympathetic Reinnervation is Required for Mammalian Cardiac Regeneration

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ian A White ◽  
Julie Gordon ◽  
Wayne Balkan ◽  
Joshua M Hare
Keyword(s):  
Sympathetic Innervation ◽  
Cardiac Regeneration ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Neonatal Mouse ◽  
Left Ventricular Myocardium ◽  
Autonomic Nerves ◽  
Mouse Heart ◽  
Minimal Scarring ◽  
Age Related

Rationale: Established animal models of tissue and limb regeneration demonstrate a critical dependence on concurrent reinnervation by the peripheral nervous system. The abundance of autonomic nerves in the mammalian heart suggests they play a similar role in the response to cardiac injury. Objective: To test the hypothesis that reinnervation is required for innate neonatal cardiac regeneration. Methods and Results: Crossing Wnt1:cre transgenic mice with a double-tandem (td) tomato reporter strain identified all neural crest-derived cell lineages including the peripheral autonomic nerves in the heart. Whole mount epi-fluorescence microscopy facilitated the clear resolution of subepicardial autonomic nerves in the mouse ventricles providing unprecedented detail of the subepicardial neuroanatomy of the mouse heart. We confirmed that sympathetic nerve structures envelop the entire heart, and importantly, exhibit robust re-growth into the regenerating myocardium following resection of the left ventricular apex in neonatal mice. While innervated hearts regenerate with minimal scarring to the left ventricular myocardium, we report that innate cardiac regeneration was inhibited following sympathectomy, as determined by cross-sectional percentage of viable LV myocardium (n=9, 0.87±1.4% vs. n=6, 14.05±4.4% ; p<0.01). Conclusions: Ablation of post-ganglionic sympathetic nerves blocks the innate regenerative capacity of neonatal mouse hearts. Therefore, the innate ability of the neonatal mouse heart to undergo regeneration in response to injury is dependent on sympathetic innervation of the ventricular myocardium. This finding has significant implications for adult regeneration following myocardial infarction where nerve growth is hindered by age related influences and scar tissue.

Increased heart rate accelerates norepinephrine washout from normal myocardium

1987 ◽  
Vol 253 (6) ◽  
pp. H1581-H1585 ◽  
Author(s):  
R. J. Henning ◽  
J. Cheng ◽  
A. M. Bhat ◽  
M. N. Levy
Keyword(s):  
Heart Rate ◽  
Ventricular Myocardium ◽  
Neuronal Uptake ◽  
Control Group ◽  
Inotropic Response ◽  
Sympathetic Stimulation ◽  
Uptake Mechanism ◽  
The Mean ◽  
Time Required ◽  
Experimental Group

We determined whether a change in heart rate affected the decay of the ventricular inotropic response to sympathetic stimulation in an experimental group and in a control group of anesthetized dogs. We induced complete heart block in each animal and paced the ventricles at rates of 90, 120, and 150 min-1 during two observation periods. In the experimental group, desipramine hydrochloride was given during the second period to block the neuronal uptake mechanism. The control animals did not receive desipramine during either period. The time required for the ventricular inotropic response to decay by 50% after cessation of a 2-min train of sympathetic stimulation was used as an index of the rate of norepinephrine washout from the myocardial interstitium. As we increased the pacing rate over the range of 90-150 min-1 in the experimental group, the mean decay half times (+/- SE) decreased by 36 +/- 4% (P less than 0.001) before desipramine and by 26 +/- 6% (P less than 0.001) in the presence of desipramine. These decrements in the decay half times were not significantly different from each other. The mean decay half times decreased by 36 +/- 4% (P less than 0.001) in the control dogs; the effects did not change appreciably from the first to the second observation period. We conclude that an increase in pacing frequency facilitates the washout of norepinephrine from the ventricular myocardium; this facilitation is equally pronounced regardless of whether the neuronal uptake mechanism is intact or suppressed.

Pyruvate potentiates inotropic effects of isoproterenol and Ca2+ in rabbit cardiac muscle preparations

2000 ◽  
Vol 279 (2) ◽  
pp. H702-H708 ◽  
Author(s):  
Hans-Peter Hermann ◽  
Oliver Zeitz ◽  
Boris Keweloh ◽  
Gerd Hasenfuss ◽  
Paul M. L. Janssen
Keyword(s):  
Energy Demand ◽  
Contractile Force ◽  
Potential Importance ◽  
Inotropic Response ◽  
Inotropic Effects ◽  
Individual Effects ◽  
Positive Inotropic Effects ◽  
Series Of Experiments ◽  
The Individual ◽  
Mere Addition

Catecholamines and elevated extracellular Ca2+concentration ([Ca2+]o) augment contractile force by increased Ca2+ influx and subsequent increased sarcoplasmic reticulum (SR) Ca2+ release. We tested the hypothesis that pyruvate potentiates Ca2+ release and inotropic response to isoproterenol and elevated [Ca2+]o, since this might be of potential importance in a clinical setting to circumvent deleterious effects on energy demand during application of catecholamines. Therefore, we investigated isometrically contracting myocardial preparations from rabbit hearts at 37°C, pH 7.4, and a stimulation frequency of 1 Hz. At a [Ca2+]o of 1.25 mM, pyruvate (10 mM) alone increased developed force (Fdev) from 1.89 ± 0.42 to 3.62 ± 0.62 (SE) mN/mm2 ( n = 8, P < 0.05) and isoproterenol (10−6 M) alone increased Fdev from 2.06 ± 0.55 to 25.11 ± 2.1 mN/mm2 ( P < 0.05), whereas the combination of isoproterenol and pyruvate increased Fdevoverproportionally from 1.89 ± 0.42 to 33.31 ± 3.18 mN/mm2 ( P < 0.05). In a separate series of experiments, we assessed SR Ca2+ content by means of rapid cooling contractures and observed that, despite no further increase in Fdev by increasing [Ca2+]o from 8 to 16 mM, 10 mM pyruvate could still increase Fdev from 26.4 ± 6.8 to 29.7 ± 7.1 mN/mm2( P < 0.05, n = 9) as well as the Ca2+ load of the SR. The results show that the positive inotropic effects of pyruvate potentiate the inotropic effects of isoproterenol or Ca2+, because in the presence of pyruvate, Ca2+ and isoproterenol induced larger increases in inotropy than can be calculated by mere addition of the individual effects.

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