RESUMEN
We have demonstrated the phenomenon of Са(2+)-induced hyperpolarization in the myocardium of pulmonary veins (PVs) in rats. An increase in cytoplasmic calcium [Са(2+)] i was shown to shift the resting potential (RP) in the PVs towards more negative values. The compounds inducing an increase in [Са(2+)] i , such as isoproterenol (10 µM), caffeine (5 mM), and ryanodine (0.01 µM), caused hyperpolarization of 10 ± 2, 9 ± 1.3, and 4.1 ± 2 mV, respectively. The inhibition of calcium-dependent potassium currents (IKCa) did not change RP of PVs under the control conditions and did not affect the Са(2+)-induced hyperpolarization.
Asunto(s)
Señalización del Calcio/fisiología , Calcio/metabolismo , Potenciales de la Membrana/fisiología , Miocardio/metabolismo , Venas Pulmonares/metabolismo , Animales , Cafeína/farmacología , Señalización del Calcio/efectos de los fármacos , Isoproterenol/farmacología , Potenciales de la Membrana/efectos de los fármacos , Ratones , Ratas , Rianodina/farmacologíaRESUMEN
Introduction of isoproterenol (beta-adrenoreceptor agonist) into rats is one of the widespread experimental models of heart failure. It is caused by diffuse ischemic damage of cardiomyocytes, followed by development of substitutive fibrosis. Apelin is a natural regulator of the myocardial contractility. The effects of apelin molecule fragment, apelin-12 and its more stable synthetic analogue, apelin-12-2 on cardiac contractile function of rats with isoproterenol-induced myocardial lesion (IML) and control animals has been studied in this work using invasive (catheterization of the left ventricle) and non-invasive (echocardiography and impedansometry) methods. Infusion of both peptides was made by sequentially increasing rate from 0.5 to 50 µg/kg/min. In the control group, efficacy of apelin-12 was low while apelin-12-2 moderately but significantly increased indices of myocardial contractility and relaxability. These changes were more pronounced in rats with IML and, in addition, the heart rate and LV systolic pressure increased in this group. These results correlate well with echocardiographic studies which showed increases of LV end diastolic volume, stroke volume and ejection fraction by 17-38%. These alterations are probably due to improved Ca2+ transport in cardiomyocytes, as in experiments on isolated cardiomyocytes both apelins have facilitated and improved Ca2+ removal from myoplasma. The results allow to conclude that apelin-12-2 seems to be a promising candidate for further development as a therapeutic agent in heart failure.
Asunto(s)
Hemodinámica/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Isoproterenol/toxicidad , Masculino , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/fisiopatología , Ratas , Ratas WistarRESUMEN
Introduction of isoproterenol (an agonist of beta-adrenoreceptors) to rats is one of the widespread experimental models of cardiac failure. It is caused by damage of cardiomyocytes with the subsequent development of substitutive fibrosis. The purpose of the given work was the complex characteristic of cardiac function by means of invasive and noninvasive (echocardiography and impedansometry) methods of research. Isoproterenol was injected twice with a daily interval in dozes 85, 120, 150 or 180 mg/kg. Echocardiographic study of the heart in 2 weeks revealed obvious attributes of cardiac failure (left ventricular dilatation, lowered ejection fraction) in the groups which have received high cumulative dozes of isoproterenol (300-360 mg/kg). The catheterization of the left ventricle in these groups has shown raised enddiastolic pressure, decreased maximal rate of pressure development and fall, and also lowered indices of myocardial contractility and relaxability. In the groups which have received smaller isoproterenol dozes, apparent decrease in relaxability parameters (constants of isovolumic and auxovolumic relaxation) has been revealed at only slightly changed parameters of contractility. A strong correlation between echocardiographic and invasive parameters of myocardial contractility has been found. The phase analysis of the cardiac cycle has shown a lengthening of isometric phases of contraction and relaxation, as well as duration of ejection due to shortening duration of filling of both ventricles. Cardiomyocytes isolated from hearts with obvious cardiac failure responded to electrostimulation by arrhythmic contractions and also by much slowed and incomplete removal of free Ca++ from the myoplasm. Results allow to conclude that relatively smaller extent of myocardial damage is accompanied by decreased relaxability at slightly changed contractility, while at greater degree of damage both processes fail, but delay of relaxation still prevails.