Angiotensin II (Ang II) produces a positive inotropic effect on the heart; however, its usefulness as an inotropic agent is limited because of its inherent vasoconstrictor action. We therefore designed Ang II analogues that are potent, positive inotropic agents with minimal myotropic properties. Replacement of the proline residue in position 7 with alanine reduced the pressor and vascular contr...

The positive inotropic action of blood plasma on isolated hearts has been known for a long time (Bowditch, 1871; Ringer, 1885; Clark, 1913; Hajdu, 1957; Hajdu, Leonard & Akers, 1957a; Hajdu, Weiss & Titus, 1957 b), and the observations recorded by various authors suggest that a number of different plasma components are responsible for positive inotropic activity. Hajdu et al. (1957b) isolated a...

Objective(s): Recently, we showed that some new synthetic compounds structurally related to cilostamide (4-(1,2-dihydro-2-oxoquinolin-6-hydroxy)- N-cyclohexyl-N-methylbutanamide), a selective phosphodiesterase 3 (PDE3) inhibitor, produce inotropic effect comparable to that of IBMX (3-isobutyl-1-methylxanthine), a non-selective PDE inhibitor, but with differential chronotropic effect. In this in...

There are some reports which indicate that several triazole derivatives have inotropic activity; however, the cellular site and mechanism of action at cardiovascular level is very confusing. In order, to have a clear understanding of these phenomena, a triazole derivative was synthesized to evaluate its biological activity on left ventricular pressure and characterize the molecular mechanism. T...

There are studies which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, a new estradiol derivative was synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molec...

background: selective phosphodiesterase (pde3) inhibitors improve cardiac contractility and may use in congestive heart failure. however, their proarrhythmic potential is the most important side effect. methods: in this research, we evaluated the potential cardiotonic activity of six new synthesized selective pde3 inhibitors (6-hydroxy-4-methylquinolin-2(1h)-one derivatives) using the spontaneo...

The potential functional roles of M(3) muscarinic receptors in mouse atria were examined by pharmacological and molecular biological techniques, using wild-type mice, muscarinic M(2) or M(3) receptor single knockout (M(2)KO, M(3)KO), and M(2) and M(3) muscarinic receptor double knockout mice (M(2)/M(3)KO). Real-time quantitative reverse transcriptase-polymerase chain reaction analysis showed th...

Isoproterenol increases and decreases contractile force at low and high concentrations, respectively, through beta(2)-adrenoceptors overexpressed in transgenic mouse heart (TG4), consistent with activation of both G(s) and G(i) proteins. Using TG4 hearts, we demonstrated that epinephrine behaves like isoproterenol, but norepinephrine does not. Epinephrine both increased (-log EC(50)M = 9.4) and...

Although the positive inotropic effect of cardiac glycosides correlates well with inhibition of Na+ pump activity in many preparations, digitalis at low concentrations (10(-9) to 10(-8) M) may produce an apparent stimulation of monovalent cation transport in isolated intact myocardium or produce an inotropic effect that does not correlate with pump inhibition. Digitalis is known to modify tissu...