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.

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.

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.

The effect of theophylline on amine-induced cardiac cyclic AMP and cardiac contractile force

1977 ◽  
Vol 55 (1) ◽  
pp. 98-104 ◽  
Author(s):  
Terry T. Martinez ◽  
John H. McNeill
Keyword(s):  
Cyclic Amp ◽  
Dose Response ◽  
Calcium Metabolism ◽  
Response Curve ◽  
Contractile Force ◽  
Inotropic Response ◽  
Inotropic Effects ◽  
Rat Atria ◽  
Contractile Effect ◽  
Cardiac Contractile

In the isolated electrically driven rat atria, theophylline (5 × 10−4 M) produced a small but significant increase in cyclic AMP content which was prevented by reserpine pretreatment. Theophylline was also found to exert a direct contractile effect, unrelated to cyclic AMP, in atria obtained from reserpine-pretreated animals. The norepinephrine inotropic response was attenuated after 3 min, enhanced after 15 min, and abolished after 60 min of exposure to theophylline (5 × 10−4 M). The maximum phenylephrine inotropic response was not significantly changed after 15 min of exposure to theophylline; however, there was a slight shift to the left of the phenylephrine dose–response curve. The effect of theophylline on cyclic AMP appeared to be additive with the norepinephrine and phenylephrine responses. The effect of theophylline on amine-induced cardiac cyclic AMP and contractile force showed no correlation between the contractile and the cyclic AMP effects at the different times tested. It is concluded that the inotropic effects of theophylline in rat atria are not mediated through cyclic AMP; instead, the methylxanthines may exert their effects on the heart through changes in calcium metabolism.

Contractile effects of cardiac neuropeptides in isolated canine atrial and ventricular muscles

1989 ◽  
Vol 257 (4) ◽  
pp. H1082-H1087 ◽  
Author(s):  
D. F. Rigel ◽  
I. L. Grupp ◽  
A. Balasubramaniam ◽  
G. Grupp
Keyword(s):  
Isometric Force ◽  
Contractile Force ◽  
Adrenergic Blockade ◽  
Canine Heart ◽  
Inotropic Action ◽  
Inotropic Effects ◽  
Calcitonin Gene ◽  
Positive Inotropic Effects ◽  
The Right ◽  
Ventricular Trabeculae

Contractile effects of the cardiac neuropeptides vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and neurotensin (NT) were compared with those of l-isoproterenol (ISO) in isolated canine atrial and ventricular trabeculae muscles stimulated to contract at 1 Hz. In ventricular muscles, ISO, VIP, and PHI augmented developed isometric force by approximately 100%. VIP and PHI were three times and 1/10, respectively, as potent as ISO. VIP also exhibited positive inotropic effects in atrial trabeculae. The contractile responses to VIP were unchanged after beta-adrenergic blockade with nadolol at a concentration (10 microM) that shifted the ISO dose-response curve two to three orders of magnitude to the right. In atrial and ventricular trabeculae, NPY (1 microM) attenuated contractile force by 36 +/- 8 and 30 +/- 4%, respectively. Each peptide also caused comparable increases or decreases in the rate of development of force and the rate of relaxation. CGRP and NT caused no significant changes in developed force in either atrial or ventricular muscles in concentrations up to 1 microM. Our results indicate a potential positive inotropic action of endogenous VIP and PHI and a cardiodepressant effect of endogenous NPY in the canine heart.

scholarly journals Effects of clenbuterol on contractility and Ca2+ homeostasis of isolated rat ventricular myocytes

2008 ◽  
Vol 295 (5) ◽  
pp. H1917-H1926 ◽  
Author(s):  
U. Siedlecka ◽  
M. Arora ◽  
T. Kolettis ◽  
G. K. R. Soppa ◽  
J. Lee ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Severe Heart Failure ◽  
Negative Inotropic Effect ◽  
Chronic Administration ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Inotropic Response ◽  
Left Ventricular Assist Devices ◽  
Acute Effects ◽  
Inotropic Effects

Clenbuterol, a compound classified as a β2-adrenoceptor (AR) agonist, has been employed in combination with left ventricular assist devices (LVADs) to treat patients with severe heart failure. Previous studies have shown that chronic administration of clenbuterol affects cardiac excitation-contraction coupling. However, the acute effects of clenbuterol and the signaling pathway involved remain undefined. We investigated the acute effects of clenbuterol on isolated ventricular myocyte sarcomere shortening, Ca2+ transients, and L-type Ca2+ current and compared these effects to two other clinically used β2-AR agonists: fenoterol and salbutamol. Clenbuterol (30 μM) produced a negative inotropic response, whereas fenoterol showed a positive inotropic response. Salbutamol had no significant effects. Clenbuterol reduced Ca2+ transient amplitude and L-type Ca2+ current. Selective β1-AR blockade did not affect the action of clenbuterol on sarcomere shortening but significantly reduced contractility in the presence of fenoterol and salbutamol ( P < 0.05). Incubation with 2 μg/ml pertussis toxin significantly reduced the negative inotropic effects of 30 μM clenbuterol. In addition, overexpression of inhibitory G protein (Gi) by adenoviral transfection induced a stronger clenbuterol-mediated negative inotropic effect, suggesting the involvement of the Gi protein. We conclude that clenbuterol does not increase and, at high concentrations, significantly depresses contractility of isolated ventricular myocytes, an effect not seen with fenoterol or salbutamol. In its negative inotropism, clenbuterol predominantly acts through Gi, and the consequent downstream signaling pathways activation may explain the beneficial effects observed during chronic administration of clenbuterol in patients treated with LVADs.

MIF-1 attenuates apomorphine stereotypies in adult rats after neonatal 6-hydroxydopamine

1989 ◽  
Vol 163 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Richard M. Kostrzewa ◽  
Teresa G. White ◽  
James E. Zadina ◽  
Abba J. Kastin
Keyword(s):  
Adult Rats ◽  
6 Hydroxydopamine

Differential impairment of thermogenesis in the pigeon after chemical sympathectomy

1978 ◽  
Vol 56 (4) ◽  
pp. 578-584 ◽  
Author(s):  
E. Hohtola ◽  
H. Rintamäki ◽  
R. Hissa
Keyword(s):  
Oxygen Consumption ◽  
Electrical Activity ◽  
Plasma Free Fatty Acid ◽  
Lower Body ◽  
Plasma Lactate ◽  
Chemical Sympathectomy ◽  
Ffa Metabolism ◽  
Lactate Levels ◽  
The Stability ◽  
6 Hydroxydopamine

A dose-controlled chemical sympathectomy with 6-hydroxydopamine (6-OHDA) did not disrupt thermostasis in the pigeon at +38 °C. At +6 °C, thermogenesis was impaired, but the lower body temperature and oxygen consumption were stable and vasoconstriction was normal. The stability may partly be explained by a massive release of adrenaline from the adrenals (50% in 20 min). Despite a deficit in heat production both after sympathectomy and after acute 6-OHDA, no change in muscle electrical activity was observed. Plasma free fatty acid (FFA) concentration was significantly elevated after sympathectomy, but no changes occurred in blood glucose or plasma lactate levels. The results indicate a major compensatory role for the adrenals in avian thermogenesis. They also suggest a sympathetically mediated auxiliary thermogenic mechanism independent of muscle electrical activity and coupled to FFA metabolism.

Abstract 12677: Impaired Cardiomyocyte Contractility to Angiotensin-(1-12) in a Humanized Angiotensinogen Model of Hypertension

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yixi Liu ◽  
Heng Jie Cheng ◽  
Xiaoqiang Sun ◽  
Jing Cao ◽  
Zhe Chen ◽  
...  
Keyword(s):  
Contractile Function ◽  
Ang Ii ◽  
Transgenic Rats ◽  
Inotropic Effects ◽  
Cardiomyocyte Contractility ◽  
Inotropic Responses ◽  
Myocyte Contractility ◽  
Agt Gene ◽  
Rat Genome ◽  
Dependent Mechanism

Background: Angiotensin-(1-12) [Ang-(1-12)] is a chymase-dependent source for Angiotensin II (Ang II) inotropic activity that may be impaired in a model of sustained hypertension with high cardiac Ang II content due to insertion of the human angiotensinogen (AGT) gene in the rat genome. Accordingly, we evaluated the effects of Ang-(1-12) and Ang II on myocyte contractility and [Ca 2+ ] i regulation in 9 adult male transgenic rats expressing the human AGT gene [TGR(hAGT)L1623)] and 9 SD controls. Methods: We compared LV myocyte contraction, relaxation and [Ca 2+ ] i transient ([Ca 2+ ] iT ) responses to Ang-(1-12) (4x10 -6 M) and Ang II (10 -6 M) in freshly isolated LV myocytes. Results: Myocyte contraction (dL/dt max , 109.6 vs 127.9 μm/s), relaxation (dR/dt max , 95.3 vs 107.5 μm/s) and [Ca 2+ ] iT (0.15 vs 0.24) were depressed in TGR(hAGT)L1623 rats compared to SD controls. Moreover, cell contractile and [Ca 2+ ] iT responses following exposure to Ang-(1-12) or Ang II were markedly blunted. In SD myocytes, versus baseline, Ang II or Ang-(1-12) superfusion produced significant increases in dL/dt max [Ang II: 44% vs Ang-(1-12): 34%], dR/dt max (33% vs 26%) and [Ca 2+ ] iT (31% vs 25%). Importantly, the magnitude of the responses to the two agents in TGR(hAGT)L1623 myocytes was significantly reduced. Versus the changes in SD myocytes, Ang-(1-12) caused significantly less increases in dL/dt max (22%), dR/dt max (16%) and [Ca 2+ ] iT (15%) in TGR(hAGT)L1623 myocytes . Ang II also caused similar significantly attenuated increases in dL/dt max (27%), dR/dt max (25%) and [Ca 2+ ] iT (23%). The Ang-(1-12)-induced inotropic effects were completely prevented in the presence of the inhibitory cAMP analog, Rp-cAMPS (10 –4 M, 2 hours) in both SD and TGR(hAGT)L1623 myocytes, but were further augmented only intransgenic rats after incubation of myocytes with the G i inhibitor, pertussis toxin (PTX, 2 μg/ml, 36°C, 5 hours). Conclusions: Ang-(1-12) stimulates LV myocyte contractile function and [Ca 2+ ] iT in both SD and TGR(hAGT)L1623 rats. Furthermore, we now show that the blunted inotropic responses to Ang-(1-12) and Ang II in rats expressing the human AGT gene is mediated through a cAMP-dependent mechanism that is coupled to both stimulatory G and inhibitory PTX-sensitive G proteins.

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