الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 210 |  |  |
| | | from | 210 | | |
Abstract
The precise mechanism for the risk of heart failure associated with rosiglitazone is not known till now. It is not known that whether the incidence of heart failure associated with rosiglitazone treatment is due to sodium retention and fluid accumulation or a direct cardiac depressant effect. Co-administration of digoxin with rosiglitazone may be needed in case of diabetes mellitus with congestive heart failure. This concomitant administration had no significant effect on the safety or steady-state pharmacokinetics of digoxin so pharmacodynamic interactions may be expected upon concomitant administration of rosiglitazone and digoxin. Our study was done to evaluate the cardiac effect of rosiglitazone using isolated right atria of non-diabetic and diabetic rats and the possible pharmacodynamic interactions of the concomitant administration of rosiglitazone and digoxin using in-vitro experiment (using the right atria of non-diabetic and diabetic rats). Also, we study the effect of concomitant administration of rosiglitazone and losartan which may be needed in case of diabetes with hypertension. This part of work is done to study of the effect of rosiglitazone, losartan and their combination on acetylcholine-induced relaxation, angiotensin-II-induced contraction of STZ-diabetic rats isolated aortic rings. In addition to some biochemical analysis (serum glucose, serum potassium and serum sodium levels). Also we study of the effect of rosiglitazone on the inhibitory effect of losartan against angiotensin-II-induced-contraction of diabetic rats isolated thoracic aortic rings, which may reflect the effect on blood pressure. from the study we concluded that rosiglitazone may have direct cardiac depressant effect .Also, rosiglitazone affects the pharmacodynamic properties of digoxin and reduces the arrhythmogenic effect of digoxin. Rosiglitazone may have vasodilating effect as indicated by its enhancing effects on ACh-induced relaxation and antagonistic effect on Ang-II-induced contraction of diabetic isolated thoracic aortic rings. Also, Rosiglitazone potentiates the action of AT1-receptor antagonist so concomitant administration of rosiglitazone and losartan may beneficial especially in diabetic patients with hypertension.