Involvement of nitric oxide in amiodarone- and dronedarone-induced coronary vasodilation in guinea pig heart.

Amiodarone, a powerful antiarrhythmic compound, possesses coronary and peripheral vasodilator properties. The mechanisms responsible for these effects remain incompletely understood. In the present study, the coronary effects of amiodarone and dronedarone, a non-iodinated amiodarone-like compound, were investigated in isolated guinea pig hearts perfused at constant flow with high K+ solution (40 mM).

SR 48692, a non-peptide neurotensin receptor antagonist, blocks the cardiovascular effects elicited by neurotensin in guinea pigs.

In guinea pigs anaesthetized with sodium pentobarbital, SR 48692, a non peptide neurotensin receptor antagonist blunted the blood pressure increase induced by exogenous neurotensin in a dose dependent manner. Furthermore, in isolated spontaneously beating guinea pig atria, both the tachycardia and inotropic responses induced by neurotensin were potently antagonized. SR 48692 did not show any intrinsic effect in vivo or in vitro.

Biochemical and pharmacological properties of SR 49059, a new, potent, nonpeptide antagonist of rat and human vasopressin V1a receptors.

SR 49059, a new potent and selective orally active, nonpeptide vasopressin (AVP) antagonist has been characterized in several in vitro and in vivo models. SR 49059 showed high affinity for V1a receptors from rat liver (Ki = 1.6 +/- 0.

Pharmacological characterization of SR 47436, a new nonpeptide AT1 subtype angiotensin II receptor antagonist.

SR 47436, 2-n-butyl-3-[(2'-(1H-tetrazol-5-yl)-biphenyl-4-yl) methyl]-1,3-diaza-spiro[4,4]non-1-en-4-one, is a new potent and selective AT1 angiotensin II (AII) receptor antagonist. It competitively inhibited [125I]AII binding to AT1 subtype receptors in rat liver membranes (IC50 = 1.7 nM) and did not interact with AT2 subtypes in rat adrenal cortical membranes.

Effects of SR 44866, a potassium channel opener, on action potentials of rabbit, guinea pig, and human heart fibers.

The effects of various concentrations (3 x 10(-8) - 1 x 10(-5) M) of SR 44866, a K+ channel opener, on action potential (AP) characteristics were investigated in isolated rabbit sinoatrial node (SAN), rabbit Purkinje fibers, guinea pig ventricle, human atrium, and human papillary muscle. SR 44866 (up to 1 x 10(-5) M), like cromakalim and pinacidil, did not modify SAN AP and automaticity of the rabbit heart. In atrial, Purkinje and ventricular fibers of animal and human hearts, SR 44866 did not significantly change membrane resting potential, AP amplitude, or maximum rate of phase 0 (dV/dtmax).

Effects of activation of ATP-sensitive K+ channels in mammalian ventricular myocytes.

A cromakalim analogue, SR 44866, is shown to open ATP-sensitive K+ channels in ventricular myocytes. The channels opened by SR 44866 were closed by internal ATP and had the same current-voltage relationship as ATP-sensitive K+ channels; channels closed by ATP could be opened by SR 44866. SR 44866 was effective when applied to either side of excised membrane patches and when included in the pipette during cell-attached membrane recordings.

Electrophysiological effects of penticainide (CM 7857) in isolated human atrial and ventricular fibers.

The intracellular electrophysiological properties of a new antiarrhythmic agent, penticainide (5 x 10(-6) to 5 x 10(-5) M) were studied in isolated driven human right atrial appendage and papillary muscle superfused with oxygenated Tyrode's solution. In atrial fibers, penticainide decreased the amplitude, maximum rate of rise (dV/dtmax), plateau amplitude, and duration (APD) of action potentials (AP). In ventricular fibers, the main AP modification induced by penticainide was a dV/dtmax diminution.

Electrophysiological studies of penticainide (CM 7857), a new antiarrhythmic agent, in mammalian myocardium.

The intracellular electrophysiologic properties of a new antiarrhythmic substance, penticainide, were studied in isolated rabbit, dog, and guinea pig myocardial preparations superfused or perfused with oxygenated Tyrode's solution. "Therapeutic" concentrations of penticainide (1.5 to 3 X 10(-5) M) had little effect on sinus node automaticity; sinoatrial conduction was slightly delayed.

Electrophysiological effects of diclofurime on rabbit and frog atrial heart muscle.

The effects of diclofurime on the electrical activity of the rabbit sinus node, rabbit atria and frog atrial fibres were studied using microelectrode and the double sucrose gap voltage-clamp techniques respectively. In rabbit sinus node, diclofurime (10(-7) M to 10(-6) M) decreased the action potential (AP) amplitude and maximum rate of depolarization (Vmax), increased the AP duration and slowed the sinus rate. In rabbit atria, the drug reduced the amplitude of the depolarizing phase and Vmax, lengthened the AP duration and decreased the resting membrane potential.