RESUMO
Adrenal progesterone secretion increases along with corticosterone in response to stress in male and female rats to modulate some stress responses. Here we investigated the role of sex steroids in sex differences in the progesterone response to 60 min of restraint stress in adult male and female rats. Comparisons between males and females in the progesterone response were evaluated in parallel with corticosterone responses. From day 5 to 7 after gonadectomy, female and male rats were treated with estradiol or testosterone, respectively (OVX-E and ORCH-T groups), or oil (OVX and ORCH groups). Female rats in proestrus, intact and 7 d adrenalectomized (ADX) male rats were also studied. At 10:00 h, blood samples were withdrawn via an implanted jugular cannula before (-5 min), during (15, 30, 45, 60 min) and after (90 and 120 min) restraint stress to measure plasma progesterone and corticosterone concentrations by radioimmunoassay. Intact male and proestrus female rats exhibited similar progesterone responses to stress. Gonadectomy did not alter the amount of progesterone secreted during stress in female rats but decreased secretion in male rats. Unlike corticosterone, the progesterone response to stress in females was not influenced by estradiol. In males, testosterone replacement attenuated the progesterone and corticosterone responses to stress. Basal secretion of progesterone among intact, ORCH and ADX males was similar, but ADX-stressed rats secreted little progesterone. Hence, the gonads differently modulate adrenal progesterone and corticosterone responses to stress in female and male rats. The ovaries enhance corticosterone but not progesterone secretion, while the testes stimulate progesterone but not corticosterone secretion.
Assuntos
Corticosterona/metabolismo , Estradiol/farmacologia , Progesterona/metabolismo , Restrição Física/psicologia , Estresse Psicológico , Testosterona/farmacologia , Adrenalectomia , Animais , Feminino , Masculino , Orquiectomia , Ovariectomia , Ovário/fisiologia , Proestro , Ratos , Ratos Wistar , Caracteres Sexuais , Testículo/fisiologiaRESUMO
The stress experienced during rape seems to facilitate ovulation since the pregnancy rate in raped women is higher than that resulting from consensual intercourse. Adrenal progesterone, as well as central norepinephrine, is released in stressful situations. At adequate estrogenic levels, one of the main actions of progesterone is to anticipate the preovulatory LH surge through noradrenaline release. We aimed to investigate whether acute stresses that mimic those of rape (exposure to predator, restraint and cervix stimulation) applied on the proestrus morning in female rats could release progesterone, activate the noradrenergic neurons and facilitate the occurrence of the LH surge. Female rats were submitted to jugular vein cannulation immediately following acute stress: restraint (R), exposure to cat (P), uterine cervix stimulation (CS) applied individually or in association (SA). Non-stressed rats were used as control. Blood samples were collected from 11:00-18:00 h for LH, progesterone, corticosterone and estradiol measurements. Double labeling for c-Fos and tyrosine hydroxylase (TH) was examined in A1, A2 and A6 noradrenergic neurons after stresses. The SA group showed a greater stress-induced increase in progesterone compared to the other groups and the preovulatory LH surge was anticipated and amplified. This effect of SA seems to be related to the higher number of c-Fos/TH + neurons in the A1 and A2. The effect of anticipating the preovulatory surge of LH could in part elucidate why, in raped women, conception can occur in phases of the menstrual cycle other than the ovulatory phase facilitating the occurrence of pregnancies.
Assuntos
Neurônios Adrenérgicos , Progesterona , Animais , Estradiol/farmacologia , Feminino , Humanos , Hormônio Luteinizante , Norepinefrina , Ovulação , Gravidez , Progesterona/farmacologia , Ratos , Tirosina 3-Mono-OxigenaseRESUMO
Dopamine (DA) is known as a primary regulator of prolactin secretion (PRL) and angiotensin II (Ang II) has been recognized as one brain inhibitory factor of this secretion. In this work, estrogen-primed or unprimed ovariectomized rats were submitted to the microinjection of saline or Ang II after previous microinjection of saline or of DA antagonist (haloperidol, sulpiride or SCH) both in the medial preoptic area (MPOA). Our study of these interactions has shown that 1) estrogen-induced PRL secretion is mediated by Ang II and DA actions in the MPOA, i.e. very high plasma PRL would be prevented by inhibitory action of Ang II, while very low levels would be prevented in part by stimulatory action of DA through D(2) receptors, 2) the inhibitory action of Ang II depends on estrogen and is mediated in part by inhibitory action of DA through D(1) receptors and in other part by inhibition of stimulatory action of DA through D(2) receptors.
Assuntos
Angiotensina II/fisiologia , Dopamina/fisiologia , Área Pré-Óptica/metabolismo , Prolactina/metabolismo , Angiotensina II/administração & dosagem , Animais , Estrogênios/fisiologia , Ciclo Estral/fisiologia , Feminino , Microinjeções , Ratos , Ratos Wistar , Receptores Dopaminérgicos/metabolismoRESUMO
The use of probiotics to prevent or treat mucosal inflammation has been studied; however, the combined effect of probiotics and prebiotics is unclear. The aim of this study was to test whether oral administration of a synbiotic (Simbioflora®) preparation containing Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus acidophilus and Bifidobacterium lactis plus fructooligosaccharide could help control mucosal inflammation in experimental mucositis induced by 5-fluorouracil (5-FU). Male BALB/c mice were randomly divided into six groups: control (CTL), control + prebiotic (CTL+P), control + synbiotic (CTL+S), mucositis (MUC), mucositis + prebiotic (MUC+P), and mucositis + synbiotic (MUC+S). Mice from the CTL+S, MUC+S, CTL+P, and MUC+P groups received synbiotic or prebiotic daily by oral gavage for 13 days. Mice in the CTL and MUC groups received the same volume of saline. On day 11, mice in the MUC, MUC+P, and MUC+S groups received an intraperitoneal injection of 300 mg/kg 5-FU to induce mucositis. After 72 h, all mice were euthanised. Intestinal permeability, intestinal histology, and biochemical parameters were analysed. Group MUC showed a greater weight loss and increased intestinal permeability (0.020 counts per min [cpm]/g) compared to the CTL group (0.01 cpm/g) P<0.05. Both treatments attenuated weight loss compared to the MUC group. Nonetheless, the synbiotic caused a greater reduction in intestinal permeability (0.012 cpm/g) compared to the MUC (0.020 cpm/g) and MUC+P (0.016 cpm/g) groups P<0.05. Mice in groups MUC+P and MUC+S displayed significant recovery of lesions and maintenance of the mucus layer. There were no differences in the short-chain fatty acid concentrations in the faeces between the MUC and CTL groups (P>0.05). Increased acetate and propionate concentrations were evidenced in the faeces of the MUC+P and MUC+S groups. Only the synbiotic treatment increased the butyrate concentration (P<0.05). The results indicate that administration of synbiotic can decrease mucosal damage caused by mucositis.
Assuntos
Mucosite/prevenção & controle , Simbióticos/administração & dosagem , Administração Oral , Animais , Bifidobacterium animalis/crescimento & desenvolvimento , Bifidobacterium animalis/metabolismo , Peso Corporal , Ácidos Graxos Voláteis/análise , Fezes/química , Fluoruracila/administração & dosagem , Fluoruracila/toxicidade , Trato Gastrointestinal/patologia , Lactobacillus/crescimento & desenvolvimento , Lactobacillus/metabolismo , Camundongos Endogâmicos BALB C , Mucosite/induzido quimicamente , Oligossacarídeos/administração & dosagem , Oligossacarídeos/metabolismo , Resultado do TratamentoRESUMO
Vaccinia virus (VACV) is an important pathogen. Although studies have shown relationships between probiotics and viruses, the effect of probiotics on VACV infection is unknown. Therefore, this work aims to investigate the probiotics effects on VACV infection. Mice were divided into four groups, two non-infected groups, one receiving the probiotic, the other one not receiving it, and two groups infected intranasally with VACV Western Reserve (VACV-WR) receiving or not receiving the probiotic. Viral titres in organs and cytokine production in the lungs were analysed. Lung samples were also subjected to histological analysis. The intake of probiotic results in reduction in viral spread with a significant decrease of VACV titer on lung, liver and brain of treated group. In addition,treatment with the probiotic results in attenuated mice lung inflammation showing fewer lesions on histological findings and decreased lethality in mice infected with VACV. The ingestion of Lactobacillus paracasei ST11 (LPST11) after VACV infection resulted in 2/9 animal lethality compared with 4/9 in the VACV group. This is the first study on probiotics and VACV interactions, providing not only information about this interaction, but also proposing a model for future studies involving probiotics and other poxvirus.
Assuntos
Lacticaseibacillus paracasei/fisiologia , Probióticos , Vaccinia virus/fisiologia , Vacínia/terapia , Animais , Citocinas/análise , Modelos Animais de Doenças , Ingestão de Alimentos , Inflamação/terapia , Pulmão/patologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. Most of the studies involving the role of the LC in hypercapnic ventilatory responses have been performed in males. Since ovarian steroids modulate the activity of LC neurons and females have a different respiratory response to CO2 than males, we evaluated the activity of LC noradrenergic neurons during normocapnia and hypercapnia in female and male rats with distinct sex hormone levels. Ovariectomized (OVX), estradiol (E2)-treated ovariectomized (OVX+E2) and female rats on the diestrous day of the estrous cycle were evaluated. Concurrently, males were investigated as gonad-intact, orchidectomized (ORX), testosterone (T)-treated ORX (ORX+T), and E2-treated ORX (ORX+E2). Activation of LC neurons was determined by double-label immunohistochemistry to c-Fos and tyrosine hydroxylase (TH). Hypercapnia induced by 7% CO2 increased the number of c-Fos/TH-immunoreactive (ir) neurons in the LC of all groups when compared to air exposure. Hypercapnia-induced c-Fos expression did not differ between diestrous females and intact male rats. In the OVX+E2 group, there was attenuation in the c-Fos expression during normocapnia compared with OVX rats, but CO2 responsiveness was not altered. Moreover, in ORX rats, neither T nor E2 treatments changed c-Fos expression in LC noradrenergic neurons. Thus, in female rats, E2 reduces activation of LC noradrenergic neurons, whereas in males, sex hormones do not influence the LC activity.
Assuntos
Hormônios Esteroides Gonadais/metabolismo , Hipercapnia/fisiopatologia , Locus Cerúleo/fisiologia , Caracteres Sexuais , Ar , Animais , Dióxido de Carbono/administração & dosagem , Dióxido de Carbono/metabolismo , Castração , Modelos Animais de Doenças , Feminino , Hormônios Esteroides Gonadais/administração & dosagem , Imuno-Histoquímica , Masculino , Neurônios/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
STUDY OBJECTIVE: The aim was to investigate left ventricular performance of infarcted hearts during scar formation and development of hypertrophy in the surviving myocardium. DESIGN: Hearts were perfused according to the Langendorff technique and left ventricular function curves were obtained by inserting a distensible balloon into the ventricular cavity. The isovolumetric systolic pressure was measured as diastolic pressure was changed from 0 to 25 mm Hg and during inotropic interventions produced by Ca and isoprenaline. EXPERIMENTAL MATERIALS: Hearts were obtained from albino rats of either sex, 180-250 g, killed 1, 3, 7 or 14 d after left coronary artery ligation (n = 24) or sham operation (n = 26). Normal rats (n = 6) were used as additional controls. MEASUREMENTS AND MAIN RESULTS: After infarction, there was a progressive and almost parallel displacement of the ventricular function curves toward higher diastolic pressures. The positive chronotropic response to isoprenaline was similar in infarcted and non-infarcted hearts. The inotropic response to Ca and isoprenaline, however, was significantly depressed in the infarcted hearts throughout the observation period. CONCLUSIONS: Hypertrophy in the surviving myocardium did not result in improvement of the left ventricular systolic function assessed under in vitro conditions during the first two weeks after infarction. The decreased inotropic response of the infarcted left ventricle to isoprenaline is likely to be dependent on the reduced Ca sensitivity of the surviving myocardium.
Assuntos
Cardiomegalia/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Função Ventricular Esquerda/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Cálcio/farmacologia , Modelos Animais de Doenças , Feminino , Coração/efeitos dos fármacos , Isoproterenol/farmacologia , Masculino , Contração Miocárdica/efeitos dos fármacos , Perfusão , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
Prolactin (PRL) secretion is inhibited by hypothalamic dopamine. Kisspeptin controls luteinising hormone (LH) secretion and is also involved in PRL regulation. We further investigated the effect of kisspeptin-10 (Kp-10) on the activity of tuberoinfundibular dopaminergic (TIDA) neurones and the role of oestradiol (E2 ) in this mechanism. Female and male rats were injected with i.c.v. Kp-10 and evaluated for PRL release and the activity of dopamine terminals in the median eminence (ME) and neurointermediate lobe of the pituitary (NIL). Kp-10 at the doses of 0.6 and 3 nmol increased plasma PRL and decreased 4-dihydroxyphenylacetic acid (DOPAC) levels in the ME and NIL of ovariectomised (OVX), E2 -treated rats but had no effect in OVX. In gonad-intact males, 3 nmol Kp-10 increased PRL secretion and decreased DOPAC levels in the ME but not in the NIL. Castrated males treated with either testosterone or E2 also displayed increased PRL secretion and reduced ME DOPAC in response to Kp-10, whereas castrated rats receiving oil or dihydrotestosterone were unresponsive. By contrast, the LH response to Kp-10 was not E2 -dependent in either females or males. Additionally, immunohistochemical double-labelling demonstrated that TIDA neurones of male rats contain oestrogen receptor (ER)-α, with a higher proportion of neurones expressing ERα than in dioestrous females. The dopaminergic neurones of periventricular hypothalamic nucleus displayed much lower ERα expression. Thus, TIDA neurones express ERα in male and female rats, and kisspeptin increases PRL secretion through inhibition of TIDA neurones in an E2 -dependent manner in both sexes. These findings provide new evidence about the role of kisspeptin in the regulation of dopamine and PRL.
Assuntos
Núcleo Arqueado do Hipotálamo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Estradiol/metabolismo , Kisspeptinas/fisiologia , Prolactina/metabolismo , Animais , Feminino , Hormônio Luteinizante/metabolismo , Masculino , RatosRESUMO
The changes occurring in the collagen content in the residual myocardium after infarction have been poorly studied. The aim of this study was to determine the changes in the collagen content in the right and left ventricular muscle of chronically infarcted hearts. Male albino rats were submitted to ligature of the left coronary artery to produce infarction (Inf). Controls underwent a sham surgery (Sh). Inf rats were divided into groups designed to receive chronic therapy with propranolol (Prop, 1 g/l, n = 10) or hydralazine (Hydr, 0.125 g/l, n = 10) dissolved in the drinking water. One group of Inf rats (n = 12) and the Sh group (n = 10) received no treatment. The animals were killed 1 month after surgery to obtain the cardiac wet weights and to determine protein and hydroxyproline (OH-Pro) concentrations in the right ventricle (RV) free wall and in the left ventricular remaining muscle (LV), including the interventricular septum. Inf determined a 42% increase of the RV weight to body weight ratio (Sh = 0.57 +/- 0.04 mg/g; Inf = 0.81 +/- 0.06 mg/g; p < 0.05) and a 64% increase of OH-Pro concentration (Sh = 450 +/- 25 micrograms/g; Inf = 738 +/- 32 micrograms/g; p < 0.05). In Inf hearts the LV OH-Pro concentration increased similarly as in the RV. No effect of drug therapy was observed in the LV. In the RV however, propranolol reduced the hypertrophy and the OH-Pro concentration by the same amount (around 30%). Hydr on the other hand reduced OH-Pro and tended to increase hypertrophy. We conclude that a similar collagen deposition occurs in the myocardium of both ventricles after infarction in rats. Prop and Hydr were able to partially reduce this collagen increase in the right but not in the left ventricle.
Assuntos
Colágeno/metabolismo , Hidralazina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/metabolismo , Propranolol/uso terapêutico , Animais , Masculino , Infarto do Miocárdio/metabolismo , Ratos , Ratos WistarRESUMO
Post-rest potentiated contractions have been reported to be more dependent on Ca2+ stored in intracellular sites than on transmembrane Ca2+ influx. The phenomenon was examined using toad ventricular strips contracting isometrically and superfused with Ringer solution. Toad ventricular strips did not present post-rest potentiation, a fact that may be explained by the reduced volume of the sarcoplasmic reticulum in the amphibian myocardium. Potentiated post-rest contractions were obtained after calcium influx blockade with 10 microM verapamil or 2 mM Mn2+ and the slow reduction of extracellular Ca2+ concentration obtained by slowly exchanging the bath fluid was accompanied by a progressive decrease of both steady-state and post-rest contractions. These data confirm the observations made on other species regarding the post-rest potentiation phenomenon and support the suggestion of the dependence of post-rest potentiation on activator calcium liberated from intracellular stores.
Assuntos
Cálcio/metabolismo , Cloretos , Espaço Extracelular/fisiologia , Compostos de Manganês , Contração Miocárdica/fisiologia , Animais , Bufo marinus , Manganês/farmacologia , Potenciais da Membrana/fisiologia , Verapamil/farmacologiaRESUMO
The purpose of this study was to investigate the changes of heart rate (HR) and sympathetic tone occurring after myocardial infarction. Male rats (200-250 g) were submitted to ligation of the anterior branches of the left coronary artery to produce infarction (INF, N = 26) or to sham surgery (SO, N = 24). Groups of animals (N = 6-8) were studied 1,3,7 and 15 days later. A group not submitted to surgical procedures was used as control (C,N = 6). Blood pressure and HR were measured in conscious unrestrained animals after cannulation of the femoral artery. Basal HR and mean arterial pressure (MAP) of the C group were 336 +/- 8 beats/min (bpm) and 110 +/- 3 mmHg, respectively. Similar values were observed in SO subgroups. One day after INF, HR increased to 417 +/- 9 bpm and MAP decreased to 97 +/- 2 mmHg. While MAP was unchanged for the remainder of the study, HR progressively decreased and normal HR values (360 +/- 18 bpm) were observed two weeks after INF. The sympathetic tone, which was evaluated from the reduction of HR after propranolol (2 mg/kg, iv), was increased during the tachycardic phase after INF. HR normalization paralleled the progressive reduction of sympathetic tone. The changes in HR after coronary artery ligation in rats seem to reflect the degree of sympathetic efferent activity during infarct healing.
Assuntos
Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Infarto do Miocárdio/fisiopatologia , Sistema Nervoso Simpático/fisiologia , Animais , Atropina/farmacologia , Bloqueio Nervoso Autônomo , Vasos Coronários , Ligadura , Masculino , Propranolol/farmacologia , Ratos , Fatores de TempoRESUMO
The effects of verapamil (0.3 to 30 microM) on potentiated rest contractions (PRC) were studied in isometric contractions of left ventricular papillary muscles of the rat. The post-rest potentiation was studied after rest periods of 5, 10, 15, 30, 60 and 120 s. Verapamil reduced the steady-state force and PRC in a dose-dependent manner. However, PRC were less depressed and the magnitude of this depression decreased as the rest period increased. The time constant of the recovery of steady state force after rest potentiation was shortened. These results indicate that the first PRC are less dependent on calcium entering the cell through the slow channels and apparently more dependent on an intracellular calcium store.
Assuntos
Contração Miocárdica/efeitos dos fármacos , Verapamil/farmacologia , Animais , Cálcio/metabolismo , Depressão Química , Contração Isométrica , Masculino , Potenciais da Membrana/efeitos dos fármacos , Ratos , Ratos EndogâmicosRESUMO
1. The role of the sarcoplasmic reticulum (SR) in the inotropic responses produced by changes in stimulation rate and rhythm and resting tension was investigated in the rat myocardium. 2. Rat papillary muscles contracting isometrically (basic stimulation rate = 30/min) were superfused in vitro with normal Krebs solution and after addition of ryanodine (1 microM). Post-rest potentiation was obtained after pauses of 5, 10, 15, 30, 60 and 120 s, and the stimulation rate was changed from 6 to 90 bpm. Post-extrasystolic potentiation was induced by interpolating an extra stimulus after an interval of 413 +/- 15 ms. NiCl2 (2 mM) was used to confirm that contractions obtained after SR blockade with ryanodine were activated only by sarcolemmal calcium influx. 3. In the presence of ryanodine, the post-rest potentiation phenomenon disappears and the force-frequency relationship changes from the typical force decrease produced by rate increase to force increase. Under the effect of ryanodine, resting tension increased with the increase in stimulation rate. This behavior was enhanced by reducing extracellular KCl from 5.4 mM to 1 mM. This maneuver decreases Na(+)-K(+)-ATPase and increases intracellular Na+ activity, which reduces Ca2+ extrusion through the Na(+)-Ca2+ exchange mechanism. 4. SR participation in the post-extrasystolic potentiation phenomenon is also suggested because ryanodine treatment reversed the extrasystolic force depression into potentiation. In the presence of ryanodine, blockade of Ca2+ influx with NiCl2 (2 mM) abolished isometric contractions indicating that after SR blockade contractions are mainly dependent on sarcolemmal Ca2+ influx. 5. The results suggest that the SR is involved in the genesis of post-rest potentiation and contributes to the typical force-frequency relationship of the rat myocardium and to the post-extrasystolic potentiation phenomenon. Moreover, SR activity seems to be important for the maintenance of low resting tension in the cardiac muscle, which may represent a safety factor against contractures during inotropic changes produced in rate and rhythm.
Assuntos
Coração/fisiologia , Contração Miocárdica/fisiologia , Retículo Sarcoplasmático/fisiologia , Animais , Bloqueadores dos Canais de Cálcio/metabolismo , Feminino , Frequência Cardíaca/fisiologia , Masculino , Músculos Papilares/fisiologia , Ratos , Ratos Wistar , Rianodina/farmacologiaRESUMO
We studied the in vitro mechanical performance of right ventricular strips obtained from male albino rats submitted to left coronary ligation for 30 days. The infarcted rats developed significant right ventricle hypertrophy together with a reduction of the isometric tension when compared to controls. The reduction was maintained even under positive inotropic intervention, i.e. the cumulative dose-response curves to calcium and adrenaline were displaced downward in parallel in the hypertrophied muscles. We conclude that after 30 days of left ventricle infarction the hypertrophied right ventricular myocardium presents a significant reduction of contractility.
Assuntos
Cardiomegalia/etiologia , Contração Isométrica , Contração Muscular , Contração Miocárdica , Infarto do Miocárdio/fisiopatologia , Animais , Peso Corporal , Cálcio/metabolismo , Cardiomegalia/fisiopatologia , Epinefrina/metabolismo , Masculino , Tamanho do Órgão , RatosRESUMO
1. The surviving hypertrophied muscle remaining after myocardial infarction in rats is less sensitive to extracellular Ca2+ than the normal myocardium. Since the inotropic effect of Ca2+ is modulated by sarcomere length, the present study was undertaken to determine if Ca2+ desensitization of infarcted left ventricles (LV) can be modulated by increasing the diastolic pressure (DP). 2. Rats submitted to left coronary artery ligation (N = 11) or sham-operation (N = 9) were killed 8-10 days later and their hearts perfused by the Langendorff technique. A balloon was introduced into the LV cavity to measure the isovolumic systolic pressure (ISP) produced by DP changes (0 to 25 mmHg) at three Ca2+ concentrations (0.8, 1.25 and 2.5 mM). 3. In control hearts submitted to a DP of 5 mmHg, the ISP increased from 36 +/- 3 to 63 +/- 4 and to 74 +/- 4 mmHg as external Ca2+ was changed from 0.8 to 1.25 and to 2.5 mM, respectively. In contrast, in infarcted hearts submitted to the same DP and Ca2+ concentrations, the ISP increased from 19 +/- 2 to 26 +/- 2 and to 27 +/- 3 mmHg. The depressed response to Ca2+ was not modified by increasing DP up to 25 mmHg, the greatest DP tested. At this DP, ISP increased from 75 +/- 4 to 103 +/- 5 and to 114 +/- 5 mmHg in control hearts and from 45 +/- 2 to 54 +/- 3 and to 55 +/- 4 mmHg in infarcted hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cálcio/farmacologia , Cardiomegalia/fisiopatologia , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Diástole/efeitos dos fármacos , Masculino , Ratos , Estimulação Química , Volume Sistólico/efeitos dos fármacos , Sístole/efeitos dos fármacos , Função Ventricular EsquerdaRESUMO
1. Post-rest potentiation reflects basic cellular mechanisms that control cardiac muscle contraction. Transmembrane calcium influx, the Na+/Ca2+ exchange and the function of intracellular stores that liberate activator calcium upon activation are some of the mechanisms involved. 2. Three aspects of the post-rest potentiated phenomenon were investigated, using isometrically contracting rat papillary muscles and toad ventricle strips: dependence on 1) inotropic state of steady-state contractions, 2) pause duration and Na+/Ca2+ exchange activity, and 3) the extent of transmembrane calcium influx. 3. The results suggest that the potentiated state of post-rest contractions increases linearly with the inotropic state of preceding steady-state control contractions. As the pause duration increases from 5 to 240 s, the post-rest potentiation also increases, attaining a steady level after 30-s pauses. During the pause, the Na+/Ca2+ exchange mechanism operates at an activity level that can alter the amount of activator calcium used for post-rest contractions. Interventions that increase intracellular Na+, such as the increase of the stimulation rate from 0.5 to 1 Hz or the increase of extracellular NaCl concentration to 160 mM, reduce the Na+/Ca2+ activity, increasing intracellular Ca2+ and post-rest potentiation. The decrease of transmembrane Ca2+ influx during activation increases the relative participation of the sarcoplasmic reticulum in the development of post-rest potentiation. Reduction of extracellular Ca2+ concentration from 1.25 mM to 0.25 mM or the use of 1 microM verapamil and 2 mM manganese increases the relative potentiation of post-rest contractions. This is particularly observed in toad ventricle strips since post-rest potentiation, which does not develop under control conditions, is observed after verapamil or manganese treatment. The results suggest that the excitation-contraction coupling process operating for post-rest contraction activation, unlike that operating for steady-state contraction activation, depends more on the calcium stored at intracellular sites than on transmembrane calcium influx.
Assuntos
Contração Miocárdica/fisiologia , Músculos Papilares/fisiologia , Animais , Bufo marinus , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Feminino , Transporte de Íons/efeitos dos fármacos , Masculino , Potenciais da Membrana , Ratos , Descanso , Sódio/metabolismoRESUMO
Left ventricle papillary muscles from Wistar male rats were studied before, during and after urea treatment. Urea was used at a concentration (17 mM) equivalent to a plasma level of 100 mg/dl. To verify whether these effects were produced by an increase in osmolarity, the study was repeated using 17 mM saccharose. The results showed that isometric force development decreased after washing out urea from the bath but inotropic responses to isoproterenol (IPA) and increased extracellular calcium attained values similar to those obtained before urea treatment. Thus, the percentual increments due to IPA and calcium were enhanced after urea treatment. The increased osmolarity due to saccharose did not produce any change in contraction or in the responses to inotropic interventions. It is suggested that urea modifies the excitation-contraction coupling mechanism in heart muscle, reducing the force developed at the steady state control level without reducing the responses to the inotropic interventions.
Assuntos
Contração Miocárdica/efeitos dos fármacos , Ureia/farmacologia , Animais , Cálcio/metabolismo , Isoproterenol/farmacologia , Ratos , Ratos Endogâmicos , Sacarose/farmacologiaRESUMO
The mechanical and electrical activities of Langendorff perfused isolated hearts from albino female rats were studied before and after the addition of 17 mM urea to the medium. The effect of urea on the osmolarity of the perfusing solution was evaluated by also carrying out the measurement in 17 mM saccharose. The rate of the spontaneously beating hearts did not change after urea or saccharose treatment. However, urea promoted a decrease in the left ventricle isovolumic systolic pressure and a reduction of the total QRS amplitude. Saccharose did not alter mechanical or electrical characteristics. Although the concentration of urea which reduced systolic isovolumic pressure development and altered the ECG is well below that required to modify protein conformation in vitro, our results suggest that its action could be at the sarcolemmal level.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Coração/efeitos dos fármacos , Sacarose/farmacologia , Ureia/farmacologia , Animais , Eletrocardiografia , Feminino , Concentração Osmolar , Perfusão , Ratos , Função VentricularRESUMO
Myocardial activation under depolarized conditions was studied in spontaneously beating Langendorff perfused hearts from albino rats. Depolarization was obtained increasing external potassium concentration in steps (5.4, 7.4, 10, 10.5, 11, 11.5 mM) in the perfusing solution. Left ventricular isovolumic systolic pressure and coronary flow did not change as external potassium increased, but the atrial and ventricular beat rates decreased, the latter showing a larger decline. In the electrocardiogram, the P-R interval increased as a function of external potassium and the amplitude of the QRS complex diminished as its duration increased. The majority of perfused hearts stopped pumping when external potassium was raised to 11.5 mM.
Assuntos
Circulação Coronária , Contração Miocárdica , Miocárdio/metabolismo , Perfusão , Potássio/metabolismo , Potenciais de Ação , Animais , Eletrofisiologia , Feminino , Masculino , RatosRESUMO
PURPOSE: To investigate the effects of chronic subcutaneous administration of reserpine (Res) or propranolol (Prop) on the postinfarction myocardial hypertrophy and the effects of Prop treatment on myocardial contractility in rats. METHODS: Male albino rats (3-month-old) were submitted to left coronary artery ligation to produce myocardial infarction. Rats submitted to a sham-operation were used as controls. Animals submitted to Res (0.5 mg/kg/day) were killed 8-10 days after surgery and those submitted to Prop (2.5 mg/kg twice a day) were killed 15 (G-15) or 30 (G-30) days later. Hypertrophy was evaluated according to cardiac chambers weight corrected to body weights. Isometric force (F) developed by isolated right ventricular (RV) strips was used as a contractile index. RESULTS: Atrial and RV hypertrophy were completely blocked by Res. Prop treatment did not significantly change infarct extension, evaluated by the fibrous scar area. Prop therapy also reduced atrial and RV hypertrophy. This effect was less intense compared to Res, however. In the G-30, for example, the relative right atrial and RV weights (mg/g) were 0.10 +/- 0.01 and 0.59 +/- 0.03 in sham-operated animals (n = 9), 0.12 +/- 0.01 and 0.079 +/- 0.07 in infarcted animals with Prop (n = 11) and 0.22 +/- 0.03 and 1.11 +/- 0.07 in those infarcted and treated with saline solution (n = 11). Basal F values were 25 to 30% lower in RV strips from infarcted than in sham-operated hearts. This reduction however was only 4% (G-15) and 8% (G-30) in infarcted hearts under Prop treatment. CONCLUSION: These data show that sympathetic blockade reduces the postinfarction myocardial hypertrophy and tends to preserve contractility of the surviving myocardium.