RESUMO
Elevated plasma endothelin-1 [ET-1] levels in both normotensive diabetic patients and streptozotocin [STZ]-induced diabetes have been reported before. ET-1 has been demonstrated to have a potent hypertrophic effect in cultured ventricular [LV] myocytes however, there is noevidence of altered ET1 production in the hypertrophied heart. Recent studies suggest that ovation in local LV expression of ET-1 mRNA may be associated with morphological and dynamic changes in diabetes mellitus [DM]. To test local LV ET1 mRNA expression in both insulin treated and nontreated diabetic animal models, explore its possible relation to LV hypertrophy [LVH], and assess some hemodynamic parameters in this pathophysiologic state. Results were compared to those obtained from normal healthy control animals of the same strain. DM was induced in 2 groups [dm-8 and dm-0] of 3 month Sprague Dawley rats [n=20 per group, blood glucose 693 +/- 101 and 592 +/- 87 mg/dl] by intraperitoneal injection of STZ [60 mg/Kg]. Insulin therapy was given to rats of dm-8 group. Rats of group dm-0 were left without treatment. Findings were compared to normal Sprague Dawley controls [n=11, blood glucose 125 +/- 20 mg/dl]. All were followed for 8 weeks, and a terminal hemodynamic stud] was performed with mean aortic flow [MAF, ml/min], mean aortic pressure [MAP, mmHg], heart rate [bpm]. Systemic arterial resistance [SAR, units] was derived. LV tissue was harvested at -80 dgree C. LV wet weight was determined and LV weight / body weight index [LVwgt./b.wgt., mg/gm] was derived. Following dot-blot autoradiographic analysis and quantitative densitometry. ET-1 mRNA was expressed as a ratio of control G3PDH mRNA. The MAP did not reveal significant difference in the 3 groups. MAP was significantly reduced in both diabetic groups with significantly reduced SAR in untreated diabetic rats. Untreated diabetic rats developed significant LVH compared to treated diabetics and normal controls. LVET1 mRNA expression was significantly greater in insulin treated group. No significant difference between normal and untreated diabetics regarding their LV mRNA encoding for ET1. In the lab animal model, IDDM was associated with LVH apparently secondary to volume overload due to systemic vasodilation. This LVH was prevented by insulin treatment. However, insulin as a growth factor increased LV ETlmRNA expression. This wrrants further research particularly in type II DM which is usually associated with hyperinsulinemia