Differential sensitivity of diabetic rat papillary muscles to negative inotropic effects of oxybarbiturates versus thiobarbiturates.
The negative inotropic effects of oxybarbiturates and thiobarbiturates were examined in papillary muscles isolated from streptozotocin-induced diabetic rats and in papillary muscles from age-matched control rats. The muscles from diabetic rats exhibited less negative inotropic responses to pentobarbital and secobarbital than the muscles from control rats. Conversely, the negative inotropic responses to thiopental and thiamylal were significantly enhanced in diabetic muscles. Differences in sensitivity to pentobarbital between control and diabetic muscles became less marked by treatment with ouabain or by lowering [Na+]o. Enhancement of the negative inotropic effect of thiamylal observed in diabetic muscles remained unchanged with these treatments. In both control and diabetic muscles, the negative inotropic effect of pentobarbital was completely reversed by increasing [Ca2+]o, but the effect of thiamylal was only partially reversed. These results suggest a difference in mechanism of action involved in establishment of the negative inotropic effects of oxybarbiturates vs thiobarbiturates. Oxybarbiturates appear to exclusively reduce the influx of extracellular Ca2+, whereas thiobarbiturates appear to affect Ca2+ movements at the Ca2+ storage sites in addition to the Ca2+ influx inhibition.
Hattori
Y
Y
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Azuma
M
M
Kemmotsu
O
O
Kanno
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012631:Secobarbital / Q000494:pharmacology*; D013840:Thiamylal / Q000494:pharmacology*; D013874:Thiopental / Q000494:pharmacology*
D013840:Thiamylal; D012631:Secobarbital; D010424:Pentobarbital; D013874:Thiopental; D002118:Calcium