Change in systemic hemodynamics after acute administration of diazepam binding inhibitor (DBI) and after autoimmunization against DBI

Endogenous peptide DBI inhibits the activity of HABA-ergic system and that is why can be a factor of arterial hypertension development. We investigated DBI influence on cardiac index (CI), arterial pressure (AP) and heart rate (HR) in rats. I.v. administration of DBI caused dose--dependent increase in CI, AP but HR did not change. High dose (150 mg/kg) caused a biphasic answer: hyperkinetic reaction reversed to cardiodepressive one. Long-term immunization against DBI led to decrease of AP and systemic vessel's resistance.     

Decreased proportion of type I myofibers in skeletal muscle of dogs with chronic heart failure

BACKGROUND: Whether biochemical and histological abnormalities of skeletal muscle (SM) develop in patients with chronic heart failure (HF) remains controversial. In the present study, dogs with chronic HF were used to examine potential alterations of SM fiber type, fiber size, number of capillaries per fiber (C/F), beta-adrenergic receptor density (Bmax), and fiber ultrastructural integrity. METHODS AND RESULTS: HF was produced in 17 dogs by sequential intracoronary microembolizations. Biopsies of the lateral head of the triceps muscle were used in all studies. Type I and type II fibers were differentiated by myofibrillar ATPase (pH 9.4 or 4.2). Bmax was assessed by radioligand binding and SM ultrastructure by transmission electron microscopy. Comparisons were made with biopsies obtained from nine control dogs. The percentage of SM type I fibers was reduced in HF dogs compared with control dogs (19 +/- 2% versus 32 +/- 5%) (p < 0.001), whereas the percentage of SM type II fibers was increased (81 +/- 2% versus 68 +/- 5%) (p < 0.001). The change in fiber type composition was not associated with a preferential atrophy or hypertrophy of either fiber type. There was no difference in SM Bmax (198.9 +/- 14.3 versus 186.8 +/- 17.3 fmol/mg protein) or in C/F (5.37 +/- 0.26 versus 5.84 +/- 0.21) between HF dogs and control dogs. No ultrastructural abnormalities were present in SM fibers of HF dogs. CONCLUSIONS: In dogs with HF, there is a decrease in the relative composition of the slow-twitch type I SM fibers and an increase in fast-twitch type II fibers. The shift in fiber type composition is not associated with preferential atrophy of either fiber type or with a reduction in C/F, beta-adrenergic receptor density, or structural abnormalities of the myofibers.     

Intermediate filament-mediated stretch-induced changes in chromatin: a hypothesis for growth initiation in cardiac myocytes

Excessive stretching of the myocardium leads to hypertrophy, but how the stretch message is communicated to hypertrophy-initiating genes is unknown. Candidates hypothesized as couplers of physical stretch to growth initiation include neural and hormonal factors, stretch-activated and stretch-inactivated ion channels, microtubules, microfilaments, and contractile activity. Upon investigation, however, all were ruled out. We provide evidence here that it is the intermediate filaments in the mechanically stressed myocyte that transmit the stretch message to the chromatin. Using rat myocytes and an immunogold desmin-lamin-labeling technique, we found that when cardiac myocytes are stretched there are changes in the spatial arrangement of both the desmin-lamin intermediate filament network and the nuclear-envelope-associated chromatin. We hypothesize that (a) by physically linking the sarcomere to chromatin, the desmin-lamin intermediate filament network couples sarcomere length to chromatin distribution, and (b) stretch-induced changes in chromatin (mediated by the intermediate filament network) activate hypertrophy-associated genes. Further investigation is needed to test this hypothesis.