Involvement of alpha-adrenergic receptors in the regulation of inotropy in the isolated rat heart

Abstract

Background. Although activation of 1-adrenergic receptors is not required for myocardial contractility, 1-adrenergic receptors can provide significant support for myocardial inotropy in various heart diseases. Aim. To study the participation of 1A- and 1B-adrenergic receptors in the force contraction regulation of the left ventricle of an isolated rat heart. Material and methods. Isolated hearts of 20-week-old rats were perfused with KrebsHenseleit solution according to the Langendorff method. The most important indicator of the inotropic function of the heart, the pressure developed by the left ventricle, was recorded using a latex balloon placed in the cavity of the left ventricle. At the 1st stage of the work, the effects of blockers of 1-adrenergic receptor subtypes on the force of contractions of an isolated heart were evaluated. At the 2nd stage, the effect of non-selective stimulation of 1-adrenergic receptors by methoxamine was studied. At the 3rd stage, the effect of methoxamine was evaluated against the background of selective blockade of 1A- or 1B-adrenergic receptors. Statistical analysis of data was performed using Statistica 6.0 software. The significance of changes between dependent data was assessed using the Wilcoxon test. To assess the differences between two sets of independent data, the MannWhitney U-test was used. Changes were considered statistically significant at p 0.05. Results. Infusion of the 1A-adrenergic blocker WB4101 at a concentration of 106 mol/l led to an increase in the force of contraction of the isolated heart by 5.6% (p=0.048). Blocker of 1B-adrenergic receptors chloroethylclonidine dihydrochloride at a concentration of 108 mol/l caused a decrease in the force of contraction of the heart by 15% (p=0.046). Stimulation of 1A-adrenergic receptors with methoxamine (108 mol/l) led to a decrease in pressure developed by the left ventricle of an isolated heart by 47% (p=0.002). Preliminary blockade of 1A-adrenergic receptors significantly reduced the severity of the negative inotropic effect of methoxamine on the left ventricular myocardium. Preliminary blockade of 1B-adrenergic receptors changed the direction of the inotropic effect of methoxamine on the myocardium of the left ventricle of an isolated heart. Conclusion. Non-selective stimulation of 1-adrenergic receptors by methoxamine leads to a significant decrease in cardiac inotropy, while preliminary blockade of 1A- or 1B-adrenergic receptors reduces the severity of this effect.