Abstract
1. This study was designed to investigate the mechanism(s) of the negative inotropic effects of alpha1-adrenoceptor agonists observed in rat isolated left atria after exposure to free radicals. 2. Ouabain and calphostin C were used in contraction experiments to block the sodium pump and protein kinase C. Methoxamine-induced phospholipase C and Na+/K+ ATPase activities were measured. 3. Methoxamine (300 microM) increased contractile force by 1.6 +/- 0.2 mN in control atria but decreased contractile force in electrolysis-treated atria by 2.0 +/- 0.1 mN (P < 0.05), as determined 10 min after methoxamine addition. In contrast, the positive inotropic effects of endothelin-1 (30 nM) and isoprenaline (10 microM) were reduced from 2.6 +/- 0.3 to 1.3 +/- 0.1 mN and from 2.6 +/- 0.3 to 1.7 +/- 0.2 mN, respectively, by electrolysis treatment (P < 0.05), but not converted into a negative inotropic action. 4. In an inositol phosphate assay we observed that the stimulation of phospholipase C by methoxamine was attenuated by electrolysis when the (electrolyzed) medium from the organ bath was used, but the phospholipase C responses were restored by the use of fresh medium. However, fresh medium did not counteract the negative inotropic effect ...Continue Reading
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