Positive inotropic effect of DPI 201-106 in spontaneously hypertensive rats: lack of inhibition by adenosine and cholinergic agents.

The positive inotropic effect of DPI 201-106 has been studied in isolated, electrically driven papillary muscles of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WK). The positive inotropic effect of isoprenaline (Iso) and Ca2+ was studied for comparison. The maximal positive inotropic effect of Iso was less in SHR than in WK. In SHR, DPI 201-106 more effectively increased force of contraction than Iso. The positive inotropic effects of DPI 201-106 and Ca2+ were not different in SHR and WK. The EC50 values of DPI 201-106, Iso, and Ca2+ did not differ in either group. Furthermore, adenosine and carbachol reduced the positive inotropic effect of Iso but failed to exert a negative inotropic action when force of contraction has been increased with DPI 201-106. The isoprenaline-antagonistic effect of adenosine and carbachol was not different in SHR and WK. We conclude that DPI 201-106 might be an effective positive inotropic agent in states in which adrenergic function is compromised. The lack of inhibition by adenosine or m-cholinoceptor agonists could contribute to the effectiveness of the compound to increase myocardial force of contraction.