Lusitropic effect and modifications of contraction-relaxation coupling induced by alpha-adrenergic stimulation in rat...

Phenylephrine (PE) and metaraminol (MR) were studied alone at 2 x 10(-5) M and at 4 x 10(-5) M respectively. These drugs were also used both in the presence of either propranolol (PR) at 4 x 10(-7) M (PE/PR and MR/PR groups) or prazosin (PZ) at 2 x 10(-7) M (PE/PZ and MR/PZ groups). Specific alpha-adrenergic stimulation (AS) was induced in the PE/PR and MR/PR groups. These AS were evaluated in isotonic and isometric conditions on rat left ventricular papillary muscle. Peak shortening velocity (Vcmax) and peak lengthening velocity (Vrmax) were calculated from the twitch with preload only. Positive (+dF/dtmax) and negative (-dF/dtmax) peak derivative forces were calculated from the isometric twitch. Two coefficients R1 and R2 were used to measure the coupling between contraction and relaxation at low and heavy load, respectively: R1 = Vcmax/Vrmax and R2 = (+dF/dtmax)/(-dF/dtmax). In all groups, there was a significant positive inotropic effect. As compared to control values before AS, R1 significantly decreased in all groups, (PE/PR: -15%; MR/PR: -18%; PE/PZ: -8%; MR/PZ: -23%; PE: -19%; MR: -32%). On the other hand, R2 significantly decreased only in three groups (PE/PZ: -5.4%; MR/PZ: -16.5%; MR: -12.0%) whereas it did not significantly change in the three other groups (PE/PR; MR/PR; PE). In all groups, and at low load, Vrmax increased more than Vcmax (positive relaxant effect i.e. R1 decreased). At heavy load, despite the positive inotropic effect, there was no significant relaxant effect after predominent alpha-AS. These results indicate that alpha-AS modified the coupling between contraction and relaxation differently, depending on the level of load.