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Muscle LIM protein (MLP) can be found at the Z-disk of sarcomeres where it is hypothesized to be involved in sensing muscle stretch. Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function. Loss of MLP in Drosophila (mlp84B) also leads to muscle dysfunction, providing a model system to examine MLP's mechanism of action. Mlp84B-null flies that survive to adulthood are not able to fly or beat their wings. Transgenic expression of the mlp84B gene in the Mlp84B-null background rescues flight ability and restores wing beating ability. Mechanical analysis of skinned flight muscle fibers showed a 30% decrease in oscillatory power production and a slight increase in the frequency at which maximum power is generated for fibers lacking Mlp84B compared with rescued fibers. Mlp84B-null muscle fibers displayed a 25% decrease in passive, active, and rigor stiffness compared with rescued fibers, but no significant decrease in isometric tension generation was observed. Muscle ultrastructure of Mlp84B-null muscle fibers is grossly normal; however, the null fibers have a slight decrease, 11%, in thick filament number per unit cross-sectional area. Our data indicate that MLP contributes to muscle stiffness and is necessary for maximum work and power generation. [ABSTRACT FROM AUTHOR]

The objectives of this study were to determine the effects of chronic angiotensin H (ANG II) infusions on ANG II content and angiotensinogen expression in the mouse kidney and the role of the angiotensin II type 1 receptor (AT1R) in mediating these changes. C57BL/6J male mice were subjected to ANG II infusions at doses of 400 or 1,000 ng·kg-1 min-1 either alone or with an AT1R blocker (olmesartan; 3 mg·kg-1·day-1) for 12 days. Systolic and mean arterial pressures were determined by tail-cuff plethysmography and radiotelemetry. On day 13, blood and kidneys were collected for ANG H determinations by radioimmunoanalysis and intra-renal angiotensinogen expression studies by quantitative RT-PCR, Western blotting, and immunohistochemistry. ANG II infusions at the low dose elicited progressive increases in systolic blood pressure (135 ± 2.5 mmHg). In contrast, the high dose induced a rapid increase (152 ± 2.5, P <0.05 vs. controls, 109 ± 2.8). Renal ANG II content was increased by ANG II infusions at the low dose (1,203 ± 253 fmol/g) and the high dose (1,258 ± 173) vs. controls (499 ± 40, P < 0.05). Kidney angiotensinogen mRNA and protein were increased only by the low dose to 1.13 ± 0.02 and 1.26 ± 0.10, respectively, over controls (1.00, P < 0.05). These effects were not observed in mice infused at the high dose and those receiving olmesartan. The results indicate that chronic ANG II infusions augment mouse intrarenal ANG II content with AT1R-dependent uptake occurring at both doses, but only the low dose of infusion, which elicited a slow progressive response, causes an AT1R-dependent increase in intrarenal angiotensinogen expression. [ABSTRACT FROM AUTHOR]