RESUMO
We performed a comparative analysis of the effect of α2-adrenoreceptor stimulation on the performance of Langendorff-isolated heart from rats with experimental myocardial infarction in the acute stage and sham-operated animals (control). In animals with peracute myocardial infarction, different agonist concentrations (clonidine, 10-6 and 10-9 M) produced a multidirectional effect on the left-ventricular developed pressure and speed and time parameters of heart contractility. In control rats, both concentrations of the agonist added to the perfused solution reduced contraction force. Clonidine in a concentration of 10-6 M reduced HR in both groups and in a concentration of 10-9 M, it decreased HR in control rats and caused multidirectional changes in rats with myocardial infarction. The coronary flow decreased in all series of experiments.
Assuntos
Clonidina , Infarto do Miocárdio , Ratos , Animais , Clonidina/farmacologia , Coração , Infarto do Miocárdio/tratamento farmacológico , Frequência Cardíaca/fisiologia , Contração MiocárdicaRESUMO
We studied the effect of selective α2C-adrenergic receptor antagonist JP-1302 in concentrations of 10-9-10-6 M on inotropy, chronotropy, and coronary flow in the Langendorff-isolated rat heart. JP-1302 in all studied concentrations decreased the left-ventricular myocardium force contraction, HR, and coronary flow. The maximum inotropic, chronotropic, and vascular effects were observed when the antagonist was applied to the perfused solution in a concentration of 10-7 M. The least pronounced decrease in the studied parameters was observed at JP-1302 concentrations of 10-8 and 10-9 M. The obtained data indicate the participation of this subtype of α2-adrenergic receptors in the regulation of activity of isolated adult rats heart.
Assuntos
Ventrículos do Coração , Miocárdio , Ratos , Animais , Contração Muscular , Receptores Adrenérgicos , Coração , Contração Miocárdica , Frequência CardíacaRESUMO
We studied the effect of the α2-adrenergic receptor agonist clonidine hydrochloride (10-9-10-6 M) on the isolated heart of adult rats after 30-day restriction of motor activity. In hypokinetic rats, in comparison with control animals, clonidine caused a positive inotropic effect; the dynamics of coronary flow was changed after stimulation of α2-adrenergic receptors by clonidine in the minimum and maximum concentrations. Moreover, clonidine in concentrations of 10-8 and 10-7 M reduced coronary flow both in the control group and against the background of hypokinesia. Clonidine (10-8-10-6 M) had a negative chronotropic effect in control and hypokinetic animals, while the dynamics of HR was multidirectional, i.e. either an increase or decrease in the effects was observed depending of the agonist concentration. Overall, the data obtained indicate the participation of α2-adrenergic receptors in adaptive processes after motor activity limitation.
Assuntos
Adrenérgicos , Clonidina , Ratos , Animais , Clonidina/farmacologia , Hipocinesia , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Receptores Adrenérgicos , Receptores Adrenérgicos alfa 2RESUMO
We studied the effect of α2-adrenoreceptor activation after preliminary If-current blockade on the performance of the Langendorff-isolated rat heart 54 days after modeling myocardial infarction. Stimulation of α2-adrenoreceptors against the background of application of If blocker ZD7288 in concentrations of 10-9 and 10-5 M decreased myocardial inotropy in isolated rat hearts by 50 and 39% (p<0.05) and increased HR by 20 and 15% (p<0.05), respectively. Activation of α2-adrenoreceptors against the background of application of ZD7288 in a concentration of 10-9 and 10-5 M led to a decrease in the coronary flow in the isolated rat heart with the model of myocardial infarction by 21% (p<0.05) and 32% (p<0.05), respectively.
Assuntos
Infarto do Miocárdio , Receptores Adrenérgicos alfa 2 , Ratos , Animais , Infarto do Miocárdio/tratamento farmacológicoRESUMO
A comparative analysis of functioning of Langendorff-isolated heart from intact rats, sham-operated rats, and rats with a model of myocardial infarction one day after ligation of the left coronary artery was carried out. No significant differences in inotropic and chronotropic functions of the heart were found in the groups of intact and sham-operated animals. In the group of rats with the myocardial infarction model, an increase in HR and a decrease in the maximum contraction and relaxation rates and left-ventricular developed pressure were shown in comparison with the groups of intact and sham-operated animals. At the same time, in the group of sham-operated animals, a decrease in coronary flow and temporal parameters of contraction was observed.
Assuntos
Infarto do Miocárdio , Animais , Ratos , Coração , Contração MiocárdicaRESUMO
We carried out a comparative analysis of the performance of the heart isolated from healthy rats and in 54 and 120 days after modeling of myocardium infarction. On day 120, the blood supply and heart contraction force increased, while HR did not change. Stimulation of α2-adrenoreceptors with clonidine hydrochloride (10-9 M) reduced the force and rate of contraction and the blood flow in the isolated heart from healthy rats. Stimulation of α2-adrenoreceptors of the isolated heart on day 54 after modeling of myocardium infarction induced a positive inotropic response, bradycardia, and insignificant changes in the heart blood flow. On day 120, stimulation of α2-adrenoreceptors slightly reduced HR and the force of contraction and induced biphasic changes in the coronary flow of the isolated heart.
Assuntos
Coração , Infarto do Miocárdio , Animais , Clonidina/farmacologia , Frequência Cardíaca , Hemodinâmica , Contração Miocárdica , Infarto do Miocárdio/tratamento farmacológico , RatosRESUMO
We studied the effect of α2-adrenoreceptor antagonist yohimbine in concentrations of 10-9-10-6 M on the inotropy, chronotropy, and coronary flow of the Langendorff-isolated rat heart. It was found that antagonist of α2-adrenoreceptors yohimbine changes all the studied parameters of the isolated heart. The force of left ventricular myocardial contraction, HR, and coronary flow decreased after application of all concentrations of α2-adrenoreceptor antagonist. The maximum inotropic, chronotropic, and vascular effects were observed when the antagonist was applied to the perfused solution in a concentration of 10-9 M. The minimum decrease in coronary flow and HR was observed when yohimbine was applied in a concentration of 10-8 M; minimum effect on myocardial contractility was revealed at α2-adrenoreceptor blocker concentration of 10-7 M.
Assuntos
Coração , Miocárdio , Animais , Frequência Cardíaca , Contração Miocárdica , Ratos , Receptores Adrenérgicos , Transdução de SinaisRESUMO
We studied the effects of the α2-adrenergic receptor antagonist yohimbine (10-9-10-6 M) on inotropy, chronotropy, and coronary flow in the Langendorff-isolated heart from 3- and 6-week-old rats. Yohimbine affected all the studied functional parameters of the isolated heart. The force of contraction of the left ventricular myocardium, HR, and coronary flow decreased at all studied concentrations of the antagonist. The maximum chronotropic effect was observed in the heart from 6-week-old rats in the presence of 10-6 M yohimbine in the perfused solution and in the heart from 3-week-old rats in the presence of 10-9 M yohimbine. The minimum chronotropic and inotropic effect was recorded in the hearts from 6-week-old animals after application of 10-9 M α2-adrenergic receptor blocker and in the hearts from 3-week-old animals at yohimbine concentration of 10-7 M. The least pronounced decrease in coronary flow in 3- and 6-week-old rats was observed at the minimum concentration of yohimbine.
Assuntos
Coração , Contração Miocárdica , Ratos , Animais , Miocárdio , Ioimbina/farmacologia , Receptores Adrenérgicos , Frequência Cardíaca/fisiologiaRESUMO
The concentration dependenies of the chronotropic response and changes in blood supply to the isolated heart of 7-day-old newborn rats induced by application of α2-adrenergic receptor agonist clonidine hydrochloride in concentrations of 10-9-10-6 M were revealed. The minimum concentration of α2-adrenergic receptor agonist caused tachycardia, while higher concentrations led to bradycardia. The maximum effect manifesting in a decrease in coronary flow was recorded at the minimum concentration of the agonist, while the highest concentration had no effect on the coronary flow. When comparing these results with those obtained in control adult rats, we found that the most pronounced differences in the chronotropic effects were observed after addition of the minimum concentration of the α2-adrenergic receptor agonist: bradycardia in adult rats and tachycardia in newborns. The maximum differences in coronary flow parameters were observed after addition of α2-adrenergic receptor agonist in the maximum concentration that induced a two-phase response in adult rats and had no effect on the blood supply in newborns.
Assuntos
Clonidina/farmacologia , Coração/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Animais Recém-Nascidos , Animais não Endogâmicos , Células Cultivadas , Frequência Cardíaca/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Perfusão , Ratos , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/metabolismoRESUMO
The study examined the effects of α1A-adrenoceptor stimulation on chronotropic function of Langendorff-perfused isolated heart ex vivo and on cardiac chronotropy in vivo in 7-day-old rats. α1A-Adrenergic receptor agonist A-61603 reduced heart chronotropy only in the whole organism. No chronotropic effects of selective stimulation of α1A-adrenergic receptors on isolated hearts were observed in ex vivo experiments. These findings suggest that α1A-adrenergic receptors are not implicated in HR regulation in newborn rats. Bradycardia induced by activation of these receptors in vivo is most likely associated with reflex influences on the heart and changes in the vascular tone in the whole organism.
Assuntos
Imidazóis/farmacologia , Receptores Adrenérgicos alfa 1/metabolismo , Tetra-Hidronaftalenos/farmacologia , Animais , Animais Recém-Nascidos , Frequência Cardíaca/fisiologia , RatosRESUMO
The study examined the effect of α2-adrenoreceptor (α2-AR) activation against the background of preliminary blockage of If on the performance of Langerndorff-isolated rat heart. Stimulation of α2-AR in isolated rat hearts against the background of ZD7288 in concentrations of 10-9 M and 3×10-5 M changed the negative dynamics of myocardial inotropy to positive (by 25 and 38%; p<0.05). Activation of α2-AR produced opposite effects on HR. If blockade abolished tachycardia caused by activation of α2-AR; HR deceleration in response to α2-AR agonist against the background of If blocker in a concentration 10-9 M was 41% (p<0.05). We observed negative dynamics of coronary flow (by 38%; p<0.05) in isolated adult rat hearts after application of α2-AR agonist against the background of If blockade (10-9 M).
Assuntos
Coração/fisiologia , Miocárdio/metabolismo , Receptores Adrenérgicos alfa 2/metabolismo , Taquicardia/tratamento farmacológico , Animais , Frequência Cardíaca/efeitos dos fármacos , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Ratos , Transdução de Sinais/fisiologia , Taquicardia/metabolismoRESUMO
The study examined the effect of clonidine hydrochloride (10-9-10-5 Ð) on electrical activity of working cardiomyocytes in rat right atrium. Stimulation of α2-adrenergic receptor with clonidine changed electrical activity of the heart. All tested concentrations of the agonist lengthened the action potential and decreased the firing rate of cardiomyocytes in a dose-dependent manner. The maximum effects of clonidine were observed at concentration of 10-5 Ð.
Assuntos
Potenciais de Ação/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Clonidina/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/fisiologia , Potenciais de Ação/fisiologia , Animais , Animais não Endogâmicos , Relação Dose-Resposta a Droga , Coração/efeitos dos fármacos , Coração/fisiologia , Átrios do Coração/citologia , Átrios do Coração/efeitos dos fármacos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/fisiologia , Ratos , Técnicas de Cultura de TecidosRESUMO
The study examined the effects of hyperpolarization-activated funny current (If) on HR and coronary flow in Langendorff-isolated hearts from newborn rats. Blockade of If current with ZD7288 changed the examined cardiac parameters. The blocker in a concentration of 10-9 M decreased HR by 26.8% (p≤0.05). In concentrations 10-8, 10-7, 10-6, and 10-5 M ZD7288 produced minor differently directed effects. In a concentration of 10-5 M, ZD7288 reduced coronary flow in the isolated heart (p≤0.01). In other concentrations, the blocker produced no significant effects on coronary flow.
Assuntos
Circulação Coronária/fisiologia , Coração/fisiopatologia , Animais , Animais Recém-Nascidos , Frequência Cardíaca , Pirimidinas/uso terapêutico , RatosRESUMO
We studied the effect of α2-adrenoreceptor agonist clonidine hydrochloride in concentrations of 10-9-10-6 M on inotropy, chronotropy, and coronary flow in Langendorff-isolated heart of adult rats. It was found that α2-adrenoreceptor agonist changed all studied parameters. Left ventricular myocardium contraction force decreased after application of all tested concentrations, the maximum effect was observed at a concentration of 10-6 M. Stimulation of α2-adrenergic receptors in concentrations of 10-8, 10-7, and 10-6 M produced a two-phase effect (initial increase and a subsequent decrease) on the coronary flow. Clonidine hydrochloride in the maximum concentration (10-6 M) caused a decrease in HR in one group and an increase in the other.
Assuntos
Agonistas Adrenérgicos/farmacologia , Clonidina/farmacologia , Circulação Coronária/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/metabolismo , Animais , Animais não Endogâmicos , Circulação Coronária/fisiologia , Relação Dose-Resposta a Droga , Coração/efeitos dos fármacos , Coração/fisiologia , Frequência Cardíaca/fisiologia , Preparação de Coração Isolado , Contração Miocárdica/fisiologia , Técnicas de Cultura de Órgãos , RatosRESUMO
Stimulation of ß-adrenoreceptors with low (10(-8) and 10(-7) M) or high (10(-6) M) doses of isoproterenol in hypokinetic rats treated with L-NAME (a non-selective blocker of NO synthases) decreased or increased myocardial contractility, respectively. In control rats, all examined doses of isoproterenol used under blockade of NO synthases inhibited myocardial contractility.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Isoproterenol/farmacologia , Contração Miocárdica/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Animais , Depressão Química , Ventrículos do Coração/efeitos dos fármacos , Imobilização , Atividade Motora , Óxido Nítrico/fisiologia , Ratos , Receptores Adrenérgicos beta/metabolismo , Estimulação Química , Função VentricularRESUMO
The study examined the effect of α1-adrenoceptor stimulation with methoxamine on chronotropic function of isolated heart perfused ex vivo according to Langendorff and cardiac chronotropy in vivo. Stimulation of α1-adrenoceptors in isolated heart induced gradually developing bradycardia, which progressed during several minutes. Similar stimulation in vivo produced a short-term bradycardia probably terminated by the compensatory influences in the whole organism. Comparison of the data obtained in both experimental paradigms during α1-adrenoceptor stimulation revealed unidirectional changes in cardiac chronotropy characterized with time-related peculiarities.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Bradicardia/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Metoxamina/farmacologia , Receptores Adrenérgicos alfa 1/metabolismo , Animais , Animais não Endogâmicos , Bradicardia/induzido quimicamente , Feminino , Coração/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Masculino , Contração Miocárdica/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Ratos , Fatores de TempoRESUMO
The study examined the dose-dependent effects of selective antagonists of α2A/D-, α2B-, and α2C- adrenoceptors applied in concentrations of 10-9-10-5 M on atrial and ventricular contractility of rat myocardium in vitro. Selective blockade of each α2-adrenoceptor subtype affected the contractile force of the atrial and ventricular strips. Various concentrations of α2A/D- and α2C-adrenoceptor antagonists produced positive inotropic effect on ventricular strips and negative effect on atrial strips. α2B-Adrenoceptor blocker in the majority of the tested concentrations produced a positive inotropic effect in both atria and ventricles.
Assuntos
Acridinas/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Idazoxano/análogos & derivados , Imidazóis/farmacologia , Contração Miocárdica/efeitos dos fármacos , Piperazinas/farmacologia , Receptores Adrenérgicos alfa 2/metabolismo , Animais , Animais não Endogâmicos , Relação Dose-Resposta a Droga , Átrios do Coração/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Idazoxano/farmacologia , Contração Miocárdica/fisiologia , Ratos , Receptores Adrenérgicos alfa 2/classificação , Técnicas de Cultura de TecidosRESUMO
The effect of verapamil-induced blockade of L-type calcium ionic currents (ICa,L) on the action of non-selective adrenergic cardiac stimulation by norepinephrine was examined during different periods of early postnatal ontogeny. In 1-week-old rats, intravenous norepinephrine induced a short-term tachycardia both with and without preliminary injected verapamil. In 3-week-old rats, norepinephrine alone produced no chronotropic effect; in contrast, it induced a biphasic tachycardia in verapamil-treated rats. In 6- and 20-month-old rats, norepinephrine induced a short-term tachycardia, which could be prevented by verapamil. The age-related peculiarities of chronotropic action of non-selective adrenergic stimulation are indicative of the role of L-type calcium ionic channels in the development of sympathetic control over the heart.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Envelhecimento/fisiologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/metabolismo , Norepinefrina/farmacologia , Receptores Adrenérgicos/metabolismo , Verapamil/farmacologia , Fatores Etários , Animais , Animais Recém-Nascidos , Animais não Endogâmicos , Coração/efeitos dos fármacos , Coração/fisiologia , Ratos , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Taquicardia/induzido quimicamente , Taquicardia/metabolismo , Taquicardia/fisiopatologiaRESUMO
Selective blockade of various α2-adrenoceptors exerts various effects on the cardiovascular system in rats. Blockade of α2A/D-adrenoceptors in experimental animals decelerates and then accelerates HR. Blockade of α2B-adrenoceptors produces a negative chronotropic effect; blockade of α2C-adrenoceptors has a positive chronotropic effect. Administration of selective blockers of α2A/D- and α2B-adrenoceptors causes hypotension, while selective blockade of α2C-adrenoceptors increases BP.