Myocardial Concentrations of Inositol and cAMP in Intact Failured Rats

[摘要] There is a paucity of data on the way (cAMP, inositol), qualitatively or quantitatively, altered in heart failure (HF). These studies were performed separately on animal models, but no study checked cAMP and inositol changes in the same animal model simultaneously. In the present study, an experimental model was used that allowed us to check both simultaneously in the same failured intact animals. Rats weighing 180-240 g and aged 8-12 weeks, underwent uninephrectomy (41 rats survived). After a 10-day observation period, DOCA was injected at 30 mg/kg s.c. once a week for 2, 3 and 5 weeks, during which period 1 % NaCl solution was given as drinking water. The blood pressure (BP) increased after 2 weeks of the treatment and uninephrectomy. After 2 weeks 8 rats were injected i.v. every 12 h with 25 micro Ci/kg (in 0.5 ml) of myo-3H-inositol. After 3 and 5 weeks another 12 and 14 rats underwent the same experiment. Samples of myocardial tissues were obtained from the anterior wall. The tissue samples were used to check the value of cellular cAMP and inositol from the same heart to check for the first time simultaneously cAMP and inositol levels in hearts from intact failured rats during different steps of HF. In addition, samples of normal myocardial tissues were obtained from 7 (controls) untreated and not nephrectomized rats. After 2, 3 and 5 weeks of treatment, all rats showed different but progressive overt signs of HF. The values of cAMP and inositol showed a not significant increase in cellular cAMP concentrations and a not significant change in DPM inositol levels in comparison with those from control tissues, while the percent values showed a significant variation, p < 0.001. The value of DPM GPI and Inos 1P showed a significant difference as well as the percent value of inositol, GPI, inositol metabolites (1P, 2P, 3P). The inositol metabolites levels showed an initial significant reduction, except for the Inos3P, and a subsequent increase in the rats treated for 3 and 5 weeks. This experimental method allowed us to study for the first time the concentrations of inositol metabolites and cAMP cellular concentrations simultaneously and in different stages of HF in intact animals. It appears that the changes of inositol metabolites happened in the first weeks after treatment, and during the subsequent weeks the values showed a light gradual recovery. The most important result of our study was the feasibility of the experimental model and the changes in inositol metabolites and cAMP concentrations during the progression of HF.

[学科分类] 心脏病和心血管学

[关键词] CAMP;Herzinsuffizienz;inositol;Kardiologie;Ratte;CAMP;heart failure;inositol;intact animals