The β-adrenoceptor site activated by CGP12177 varies in behavior according to the estrous cycle phase and stress

2003 ◽  
Vol 81 (5) ◽  
pp. 459-468 ◽  
Author(s):  
I N Santos ◽  
F K Marcondes ◽  
R C Spadari-Bratfisch
Keyword(s):  
Estrous Cycle ◽  
Stress Hormones ◽  
Serum Levels ◽  
Female Rats ◽  
Cycle Phase ◽  
Response Curves ◽  
Chronotropic Response ◽  
The Right ◽  
Right Atria ◽  
Group Serum

The aim of this work was to assess whether stress and estrous cycle phases affected the β-adrenoceptor (β-AR) site activated by CGP12177 in the right atria of rats. The chronotropic response to CGP12177 in the absence or presence of antagonists was determined in atria from rats submitted to one daily foot-shock session for 3 consecutive days. Blood was collected for hormonal assays. The pD2 for CGP12177 in atria from females was lower than in atria from males and was unaltered by stress or the estrous cycle. Propranolol (200 nM) or CGP20712A (3 μM) shifted the concentration–response curves to CGP12177 to the right in control and stressed estrus or control diestrus rats. Atria from stressed diestrus rats were resistant to blockade by propranolol or CGP20712A, indicating that the effect of β-adrenoceptor antagonists on the response to CGP12177 is influenced by estrous cycle phases. The stress-induced increase in serum corticosterone levels was independent of the estrous cycle or gender, but the estradiol/progesterone ratio was affected differently in the two groups of female rats. In the diestrus group, serum estradiol levels decreased after the first foot-shock session and remained low until the day of sacrifice, whereas in the estrus group the serum levels of estradiol did not decrease after stress and peaked on the second day, which corresponded to proestrus. These data do not indicate whether there is a direct or indirect effect of stress hormones and (or) sex steroids on cardiac β-AR sensitivity. However, they do show that the classic and low-affinity binding sites of the β-AR are independently regulated and that the β-AR atypical site affinity for antagonists depends on the estrous cycle.Key words: allosterism, β-adrenoceptor, β-adrenoceptor, receptor active site, steroid hormones, stress.

Pharmacological evidence for β2-adrenoceptor in right atria from stressed female rats

1999 ◽  
Vol 77 (6) ◽  
pp. 432-440 ◽  
Author(s):  
R C Spadari-Bratfisch ◽  
I N Santos ◽  
LCM Vanderlei ◽  
F K Marcondes
Keyword(s):  
Estrous Cycle ◽  
Model Equation ◽  
Female Rats ◽  
Cycle Phase ◽  
Response Curves ◽  
Chronotropic Response ◽  
Site Model ◽  
Stressed Female ◽  
Right Atria ◽  
Shock Stress

The purpose of the present study was to demonstrate a physiological response to TA2005, a potent β2-adrenoceptor (β2-AR) selective agonist, in right atria isolated from stressed female rats under the influence of the estrous cycle. We obtained concentration-response curves to the agonist in the presence and in the absence of selective antagonists in right atria isolated from female rats submitted to three daily foot-shock sessions (30 min duration, 120 pulses of 1.0 mA, 1.0 s, applied at random intervals of 5-25 s) and sacrificed at estrus or diestrus. Our results showed that the pD2 values of TA2005 were not influenced by estrous cycle phase or foot-shock stress. However, in right atria from stressed rats sacrificed during diestrus, the concentration-response curve to TA2005 was biphasic, with a response being obtained at concentrations of 0.1 nM, whereas during estrus no response was observed at doses lower than 3 nM. ICI118,551, a β2-AR antagonist, abolished the response to nanomolar concentrations of TA2005 in right atria from stressed rats at diestrus, with no changes in agonist pD2 values in right atria from control rats (7.47 ± 0.09, p > 0.05) but a 3-fold decrease in pD2 values of TA2005 in right atria from foot shock stressed rats (7.90 ± 0.07, p [Formula: see text] 0.05). Concentration-response curves to TA2005 in the presence of ICI118,551 were best fitted by a one-site model equation. The β1-AR antagonist, CGP20712A, shifted to the right only the second part of the concentration-response curves to the agonist, unmasking the putative β2-AR-mediated response to the agonist in tissues isolated from stressed rats at diestrus. Under this condition, concentration-response curves to the agonist were best fitted by a two-site model equation. pD2 and maximum response of TA2005 interaction with β1- and putative β2-adrenoceptor components were calculated. Schild analyses gave a pKB value for CGP20712A that was typical for the interaction with β1-AR in each experimental group. pKB values for ICI118,551 could not be obtained in stressed rats sacrificed at diestrus since Schild plot slopes were lower than 1.0. In right atria from control rats, ICI118,551 pKB values were similar to reported values for the interaction of the antagonist with β1-AR. These results confirm that a heterogenous β-AR population mediating the chronotropic response to catecholamines can be demonstrated in right atria from foot shock stressed female rats sacrificed at diestrus. The stress-induced response seems to be mediated by the β2-AR subtype. Right atria from rats sacrificed during estrus are protected against stress-induced alterations on the homogeneity of β-AR population.Key words: foot-shock stress, TA2005, ICI118,551, CGP20712A, estrus, diestrus.

Relationship among sensitivity to adrenaline, plasma corticosterone level; and estrous cycle in rats

1995 ◽  
Vol 73 (5) ◽  
pp. 602-607 ◽  
Author(s):  
M. L. V. Rodrigues ◽  
F. K. Marcondes ◽  
R. C. Spadari-Bratfisch
Keyword(s):  
Estrous Cycle ◽  
Dose Response ◽  
Corticosterone Level ◽  
Plasma Corticosterone ◽  
Female Rats ◽  
Extraneuronal Uptake ◽  
Response Curves ◽  
Experimental Conditions ◽  
Dose Response Curves ◽  
Right Atria

The dose–response curves to the chronotropic effect of adrenaline obtained in right atria isolated from female rats indicated an order of increasing sensitivity to adrenaline, at the pD2 level, according to the estrous cycle, as follows: estrus ≤ metestrus ≤ diestrus ≤ proestrus. Inhibition of neuronal and extraneuronal uptake shifted the dose–response curves to adrenaline to the left only in right atria isolated from rats during estrus or metestrus. Moreover, under these experimental conditions, right atria were subsensitive to adrenaline during proestrus, in contrast to metestrus. Plasma corticosterone levels were lower during estrus and higher at proestrus. There was a positive correlation between right atria sensitivity to adrenaline and plasma corticosterone levels and estrous cycle phases. Our results also suggest that in the rat right atria during proestrus, as opposed to the other phases of the estrous cycle, there was an endogenous inhibition of extraneuronal uptake together with some alteration at the adrenoceptor level and (or) at intracellular mechanisms beyond receptors.Key words: adrenergic response, female, adrenaline, chronotropism, right atria.

Chronotropic response to (±)-CGP12177 in right atria of stressed rats

2001 ◽  
Vol 79 (5) ◽  
pp. 393-399 ◽  
Author(s):  
I N Santos ◽  
R C Spadari-Bratfisch
Keyword(s):  
Response Curve ◽  
Response Curves ◽  
Stimulant Effect ◽  
Chronotropic Response ◽  
Stress Changes ◽  
Random Intervals ◽  
The Right ◽  
Right Atria ◽  
Concentration Response Curve ◽  
Shock Stress

Foot-shock stress changes the sensitivity of the rat right atria to β1- and β2-adrenoceptor (AR) agonists. We investigated whether the same stress protocol also changes the atrial sensitivity to the non conventional agonist, (±)-CGP12177. Concentration-response curves to (±)-CGP12177, a β1- and β2-adrenoceptor antagonist with agonist properties at the putative β4-adrenoceptors, were obtained in the absence and presence of propranolol (200 nM or 2 µM), CGP20712A 10 nM plus ICI118,551 50 nM, or CGP20712A (1 µM or 3 µM), in right atria from rats submitted to three daily foot-shock sessions (120 mA pulses of 1.0 s duration applied at random intervals of 5-25 s over 30 min) and killed after the third session. The pD2 for (±)-CGP12177 was not influenced by foot-shock stress. The stimulant effect of (±)-CGP12177 was resistant to blockade by 200 nM and 2 µM (±)-propranolol, and to combined blockade by CGP20712A and ICI118,551. However, in right atria from stressed rats given 200 nM propranolol, the concentration-response curve to the agonist was shifted 2.0-fold to the right. CGP20712A shifted the concentration-response curve to (±)-CGP12177 to the right by 4.6- (1 µM) and 19-fold (3 µM) in atria of control rats, and by 2.2- (1 µM) and 43-fold (3 µM) in atria of stressed rats. Maximum response to CGP12177 was not affected by propranolol or CGP20712A in concentrations ranging from 0.1 nM to 10 µM. These results show that the chronotropic effect of (±)-CGP12177 is mediated by atypical β4-adrenoceptors. In constrast with to β1-and (or) β2-AR, this receptor is resistant to the effects of foot-shock stress, suggesting that the putative β4-AR is a different receptor from a low affinity state of β1-adrenoceptor, as previously proposed, unless both proposed isoforms of β1-adrenoceptor show independent stress-induced behavior.Key words: putative β4-adrenoceptor, low affinity β1-adrenoceptor isoform, stress, right atria, chronotropic response.

scholarly journals Transcriptomic uniqueness and commonality of the ion channels and transporters in the four heart chambers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sanda Iacobas ◽  
Bogdan Amuzescu ◽  
Dumitru A. Iacobas
Keyword(s):  
Ion Channels ◽  
Cycle Phase ◽  
Functional Roles ◽  
Expression Control ◽  
Gene Expression Control ◽  
Left And Right ◽  
The Right ◽  
Phase Out ◽  
Right Atria ◽  
Agilent Microarrays

AbstractMyocardium transcriptomes of left and right atria and ventricles from four adult male C57Bl/6j mice were profiled with Agilent microarrays to identify the differences responsible for the distinct functional roles of the four heart chambers. Female mice were not investigated owing to their transcriptome dependence on the estrous cycle phase. Out of the quantified 16,886 unigenes, 15.76% on the left side and 16.5% on the right side exhibited differential expression between the atrium and the ventricle, while 5.8% of genes were differently expressed between the two atria and only 1.2% between the two ventricles. The study revealed also chamber differences in gene expression control and coordination. We analyzed ion channels and transporters, and genes within the cardiac muscle contraction, oxidative phosphorylation, glycolysis/gluconeogenesis, calcium and adrenergic signaling pathways. Interestingly, while expression of Ank2 oscillates in phase with all 27 quantified binding partners in the left ventricle, the percentage of in-phase oscillating partners of Ank2 is 15% and 37% in the left and right atria and 74% in the right ventricle. The analysis indicated high interventricular synchrony of the ion channels expressions and the substantially lower synchrony between the two atria and between the atrium and the ventricle from the same side.

Evaluation of β-Adrenerglc Blocking Agents in Presence of Adrenergic Tone

1972 ◽  
Vol 50 (5) ◽  
pp. 381-388
Author(s):  
Victor Elharrar ◽  
Reginald A. Nadeau
Keyword(s):  
Dose Response ◽  
Sinus Node ◽  
Stellate Ganglion ◽  
Sodium Pentobarbital ◽  
Response Curves ◽  
Chronotropic Response ◽  
Blocking Agents ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
The Right

The importance of the level of adrenergic tone in the determination of the dose–response curve to noradrenaline (NA) and in the evaluation of β-adrenergic blocking agents was studied in open-chest sodium pentobarbital anesthetized dogs by injecting drugs directly into the sinus node artery. Changes in the level of adrenergic tone by stimulating the right stellate ganglion resulted in variation of the observed chronotropic response to NA and of its ED50. The chronotropic responses were corrected by taking into account the underlying adrenergic tone. The negative chronotropic effect of dl-propranolol (1 and 10 μg) appeared to be related to its β-blocking properties and not to its quinidine-like effects as shown by the lack of effect of d-propranolol injected at the same doses. The magnitude of the negative chronotropic effects of 10 μg of propranolol and 100 μg of practolol, oxprenolol, and sotalol was shown to be related to the initial heart rate and consequently to the level of adrenergic tone. The comparison of these four β-blocking agents was carried out on corrected dose-response curves to NA. Their relative potencies were found to be: propranolol > oxprenolol > practolol > sotalol, corresponding to ratios of 1, [Formula: see text], [Formula: see text], and [Formula: see text]

scholarly journals Determination of the estrous cycle phases of rats: some helpful considerations

2002 ◽  
Vol 62 (4a) ◽  
pp. 609-614 ◽  
Author(s):  
F. K. MARCONDES ◽  
F. J. BIANCHI ◽  
A. P. TANNO
Keyword(s):  
Estrous Cycle ◽  
Cell Types ◽  
Short Length ◽  
Female Rats ◽  
Cycle Phase ◽  
Objective Lens ◽  
Vaginal Smear ◽  
Vaginal Secretion ◽  
Cellular Types

The short length of the estrous cycle of rats makes them ideal for investigation of changes occurring during the reproductive cycle. The estrous cycle lasts four days and is characterized as: proestrus, estrus, metestrus and diestrus, which may be determined according to the cell types observed in the vaginal smear. Since the collection of vaginal secretion and the use of stained material generally takes some time, the aim of the present work was to provide researchers with some helpful considerations about the determination of the rat estrous cycle phases in a fast and practical way. Vaginal secretion of thirty female rats was collected every morning during a month and unstained native material was observed using the microscope without the aid of the condenser lens. Using the 10 x objective lens, it was easier to analyze the proportion among the three cellular types, which are present in the vaginal smear. Using the 40 x objective lens, it is easier to recognize each one of these cellular types. The collection of vaginal lavage from the animals, the observation of the material, in the microscope, and the determination of the estrous cycle phase of all the thirty female rats took 15-20 minutes.

scholarly journals SUN-251 The Effects of Unilateral Vagotomy in Female Rats with Blockade of the Muscarinic System of the Suprachiasmatic Nucleus on Ovulation and Estradiol Serum Levels

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Elizabeth Vieyra-Valdez ◽  
Julio Cesar Garcia-Tabla ◽  
Hugo Alberto Zarco-Juarez ◽  
Roberto Calderon-Ramos ◽  
Leticia Morales-Ledesma ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Suprachiasmatic Nucleus ◽  
Serum Levels ◽  
Female Rats ◽  
Motor Nucleus ◽  
Exact Probability ◽  
Dorsal Motor Nucleus ◽  
Endocrine Organs ◽  
The Right ◽  
Left Vagus

Abstract Several studies show that the suprachiasmatic nucleus (SCN) participates in the regulation of the functions of various endocrine organs through multisynaptic nerve pathways. Some of these pathways communicate the SCN with the dorsal motor nucleus of the vagus and the nucleus of the solitary tract, which are part of the origin of the vagus nerve (1). Previously we demonstrated that atropine (ATR) microinjection in the right SCN on the day of the proestrus, blocks ovulation, while the same treatment in the left SCN does it partially (2). In the present study we analyzed the possibility that the vagus nerve is one of the neural ways by which the SCN regulates the secretion of estradiol (E2) in the proestrus and subsequent ovulation. For this, cyclic rats were anesthetized with ketamine-xylazine at 09.00 of the day of the proestrus. The animals were randomly assigned to one of the following groups: rats with ATR (62.5 ng diluted in 0.3 µl of saline) microinjection in the right or left SCN, followed by ventral laparotomy or ipsilateral vagotomy to the microinjection side. The animals were sacrificed 5 h after surgery, and estradiol (E2) levels were measured. Other groups of animals with the same treatments were sacrificed 24 hours after surgery, and ovulation rate and number of ova shed were evaluated. The left vagus section did not modify the effects of ATR microinjection in the left SCN on ovulatory rate (2/5 vs. 4/7) and E2 secretion (46.6±9.0 vs. 51.3±9.0, pg/ml). In animals with ATR microinjection in the right SCN, the right vagus section increased the rate of ovulating animals (6/8 vs. 2/9, p <0.0001, Fisher’s exact probability test) and E2 levels (51.8±9.4 vs. 22.4 ± 4.0, p <0.05, two-way ANOVA, followed by Tukey’s multiple comparison test). Present results suggest that the right vagus nerve plays a role in the multisynaptic communication between the right SCN and the right ovary, while the left vagus does not. Reference: (1) Travagli, R. A. J. Physiol. 2007 Jul 15:582(Pt 2):471. (2) Vieyra et al., Reproductive Biology and Endocrinology. 2016 Jun 16 14(1):34, 1-11.Supported by CONACyT 236908; DGAPA-PAPIIT IN216519

Dissociation constants (KA) and relative efficacies of sympathomimetic amines in isolated atria during hypothermia-induced supersensitivity

1983 ◽  
Vol 61 (6) ◽  
pp. 572-580 ◽  
Author(s):  
Kenneth J. Broadley ◽  
John H. McNeill
Keyword(s):  
Dose Response ◽  
Dissociation Constants ◽  
Response Curves ◽  
Isolated Atria ◽  
Adrenoceptor Agonists ◽  
Dose Response Curves ◽  
The Right ◽  
Tension Curves ◽  
Noradrenaline And Adrenaline ◽  
Right Atria

Hypothermia increases the sensitivity of isolated cardiac muscle to stimulation by β-adrenoceptor agonists. The purpose of this study was to determine pharmacologically whether this supersensitivity is associated with a change in the affinity of agonists for the receptor. The positive inotropic and chronotropic responses of guinea-pig paced left and spontaneously beating right atria were recorded. Cumulative dose–response curves to noradrenaline (or adrenaline) were compared with isoproterenol in each tissue. At 38 °C, the rate curves were to the left of the tension curves, with lower mean effective concentration (EC50) values. However, this difference was less for noradrenaline and adrenaline which were therefore tension selective relative to isoproterenol. Lowering the temperature to 25 °C induced supersensitivity, all dose–response curves being displaced to the left. In the presence of carbachol the curves were shifted to the right with depression of the maxima. Dissociation constants (KA) were calculated from plots of reciprocals of equiactive concentrations obtained before and in the presence of carbachol. KA values for rate and tension responses of each agonist were identical at 38 °C, indicating that the rate selectivity was not due to affinity differences. The efficacies (er) of noradrenaline and adrenaline were greater than isoproterenol for tension, but smaller for rate responses, which may explain their relative tension selectivity. At 25 °C the KA values of all agonists were reduced approximately 10-fold. Hypothermia-induced supersensitivity is therefore associated with an increase in affinity for the cardiac β-adrenoceptor.

Reduction of intrinsic sinoatrial frequency and norepinephrine response of the exercised rat

1977 ◽  
Vol 55 (4) ◽  
pp. 813-820 ◽  
Author(s):  
Richard L. Hughson ◽  
John R. Sutton ◽  
J. Desmond Fitzgerald ◽  
Norman L. Jones
Keyword(s):  
Sinoatrial Node ◽  
Parasympathetic Nervous System ◽  
Control Group ◽  
Response Curves ◽  
Chronotropic Response ◽  
In Vitro Measurements ◽  
The Right

Physical training is associated with a reduction of intrinsic sinoatrial activity; the present study examined the role of the parasympathetic nervous system in this reduction. Six groups of rats were studied for 10 weeks: inactive control; treadmill exercised; parasympathetic receptor blockade with atropine; exercise plus atropine; parasympathetic receptor stimulation with carbachol; and exercise plus carbachol. In vivo ISF (cardiac frequency 20 min after injection of propranolol and atropine) was measured at 3-week intervals. At the end of 10 weeks the right atrium was excised, in vitro measurements were made of ISF, and chronotropic dose–response curves to acetylcholine and norepinephrine were established. In vivo, ISF was reduced with time, the greatest reduction being found in the exercise plus atropine group; the treadmill-exercised and the atropine-treated groups also had a greater reduction than the control group. In vitro, no differences were observed in acetylcholine responses. The maximum norepinephrine chronotropic response was reduced in the treadmill-exercised and the exercise plus atropine groups. The maximum norepinephrine-induced frequency correlated with the in vitro ISF (r = 0.75). Thus, ISF was reduced with training, but this effect was independent of parasympathetic activity. The properties of the sinoatrial node which set ISF also influenced the maximum norepinephrine response.

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