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.
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000502:physiology; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D007473:Ion Channels; D010879:Piperazines; D002217:Carbachol; C046261:DPI 201-106; D000241:Adenosine; D007545:Isoproterenol; D002118:Calcium