EFFECTS OF ADENOSINE AND ISOPRENALINE IN LEFT ATRIA FROM BOTH NEONATAL AND MIDDLE-AGED NONINSULIN-DEPENDENT DIABETIC RAT MODELS

1. This study examined the ability of atria from neonatal and middle-a ged noninsulin-dependent diabetic rat models to respond to both adenos ine and isoprenaline. 2. Cumulative additions of adenosine (1-1000 mu M) produced concentration dependent decreases in the force of contract ion of rat atria that were unchanged in neonatal diabetic animals. Alt hough direct inotropic responses to adenosine were unchanged, atria fr om neonatal diabetic animals exhibited an increase in maximum response to adenosine induced antiadrenergic effect. 3. Atria from middle aged noninsulin dependent diabetic rats exhibited a supersensitivity to th e direct inotropic effect of adenosine compared with atria from age ma tched control rats. The middle aged, noninsulin dependent diabetic sta te did not alter the maximum response of atria to adenosine-induced an tiadrenergic effect. 4. A comparison was made between middle aged (IO month old) controls and young (4 month old) controls. Atria from middl e aged control animals exhibited a lower sensitivity and responsivenes s to the direct inotropic effect of adenosine compared with those from young controls. 5. Cumulative additions of isoprenaline (10(-9)-10(-6 ) M) produced concentration-dependent increases in inotropy that were unchanged in atria from either neonatal or middle aged noninsulin depe ndent diabetic rats. 6. These results show that neonatal and middle-ag ed noninsulin-dependent diabetes and age related factors lead to signi ficant changes in atrial reactivity to the adenosine-induced stimulati on in the absence and presence of isoprenaline. However; isoprenaline induced positive inotropic response cannot change in each diabetic hea rt to an apparent extent. (C) 1997 Elsevier Science Inc.