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Testing conception of engagement of imidazoline receptors in imidazoline drugs effects on isolated rat heart atria

100%

Radwanska A. , Dlugokecka J. , Wasilewski R. , Kaliszan R.

Journal of Physiology and Pharmacology

2009

tom 60

nr 1

131-142

Recently, attention has been payed to the role of imidazolines in physiology of the heart. However, no systematic comparative studies were reported regarding the activity of a representative set of specific ligands towards imidazoline receptors in the heart preparations. The aim of this project was to test effects of a set of ligands on the pharmacological function of putative imidazoline receptors in isolated rat heart atria. Known imidazoline drugs with a postulated high affinity to imidazoline I1 receptor: AGN192403, rilmenidine, moxonidine and clonidine were used. The specific ligands of imidazoline I2 receptor: 2-BFI, BU239 and putative natural ligand for imidazoline I1, I2 and I3 receptors, agmatine, were tested also. The spontaneously beating right and left atria, driven electrically, were studied. Dose-response curves for amplitude and rate of the contractions of the atria were produced by administration of increasing doses of the agents. Phentolamine as 1/2 adrenergic receptors blocker and idazoxan as I2/I1/2 receptors blocker were added in order to inhibit ino- and chronotropic effects of the compounds studied. The -log EC50 parameters were calculated. The positive inotropic effect on left atria were evoked with the rank order of potency: agmatine >> clonidine > BU239 > rilmenidine moxonidine and these effects were generally diminished by idazoxan. Moxonidine produced a weak positive inotropic effect potentiated by idazoxan. Rilmenidine and moxonidine were assumed to act as partial agonists of imidazoline I1 receptor. AGN192403 did not change the amplitude of beating of left atria. The positive chronotropic effects on spontaneously beating right heart atria were with in the following order of potency: BU239 agmatine >>> clonidine > AGN192403. Idazoxan markedly antagonized chronotropic effect of both BU239 and agmatine. 2-BFI weakly diminished the rate of beating of atria; moxonidine and rilmenidine had no effect. In conclusion, imidazoline receptors of the I1 subtype may be involved in inotropic reaction of the agents studied, but this effect depends mainly on the 2/1 adrenergic receptors. Engagement of I2 imidazoline receptors, along with the 2 adrenergic ones, in chronotropic activity of isolated right atria of rat has been demonstrated.

Simulating niflumic acid effect on sinoatrial node cells

86%

Cieniawa J.

Biocybernetics and Biomedical Engineering

2004

tom Vol. 24, no. 3

61-65

It was recently reported that niflumic acid was capable of inhibiting the hyperpolarization-activated pacemaker current. To obtain insights into the ionic mechanisms governing niclumic acid effect on cardiac sinoatrial (SA) myocytes, computer simulations were performed based on a computer model of electrical activity of SA node cells. One cell was described by 15 nonlinear first-order differential equations that describe the time course of transmembrane potential difference, ionic concentrations, and states of the voltage gated ionic channels. The inhibition of the hyperpolarization-activated pacemaker current contributed to the chronotropic effect by reducing the rate of diastolic depolarization.

Cytochemical localization of histamine-stimulated adenylate cyclase activity in guinea pig heart tissue

72%

Schulze W. , Wollenberger A.

Folia Histochemica et Cytobiologica

1984

tom 22

nr 3-4

Thrombolytic activity of beta-adrenolytic drug, sotalol

51%

Korbut R. , Swies J. , Marcinkiewicz E. , Gryglewski R. J.

Journal of Physiology and Pharmacology

1998

tom 49

nr 1