| Autor: |
Hayes, J. Scott, Wyss, Virginia L., Wilson, Harve, Pollock, G. Donald |
| Zdroj: |
Journal of Cardiovascular Pharmacology; January 1985, Vol. 7 Issue: 1 p182-189, 8p |
| Abstrakt: |
AR-L57 and AR-L115 have been of interest as inotropic agents for management of heart failure. Although their physiological effects are well documented, their mechanism(s) of action are unclear. Both AR-L57 and AR-L115 increased contractile force of cat papillary muscles in concentration-dependent manners; these effects were independent of either α- or β-adrenoceptor stimulation. To determine if these effects occurred via a cAMP-clependent mechanism, cardiotonic actions were studied in the presence of carbachol. Muscarinic stimulation of papillary muscles attenuated contractile responses to AR-L115 thus implying a cAMP-mediated response. By contrast, carbachol did not alter the dose-response profile to AR-L57. In addition. AR-L115 potentiated the inotropic actions of isoproterenol whereas AR-L57 was ineffective. Both AR-L57 and ouabain increased diastolic resting tension in papillary muscles — a phenomenon associated with a stale of Ca2overload: AR-L115 was without effect. In anesthetized dogs. i.v. AR-L57 and AR-L115 increased contractility and heart rate while reducing mean arterial blood pressure. Both agents had similar rates of onset (10–15 s) and durations of action (40-M) mini. Although in vitro studies clearly indicate that AR-L57 and AR-L57 enhance inotropic state by distinct mechanisms, their in vivo cardiovascular profiles are comparable. |
| Databáze: |
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