Cyclic Nucleotides in Progressive Muscular Dystrophy

Abstract

The authors radioimmunoassayed cyclic nucleotide concentrations in plasma and biopsied muscles of muscular dystrophy and muscles of chicken embryo. c-AMP concentrations in plasma were significantly lowered in Duchenne-type muscular dystrophy and this lowered degree was correlated with the stage of progression. Plasma c-GMP levels were also depressed in Duchenne-type dystrophy. In biopsied muscles, c-AMP concentrations per milligram of non-collagen protein were within normal limits. Therefore, the decrease of plasma c-AMP concentrations might be an expression of total metabolic changes rather than a pathologic process of the muscle itself. As for the dystrophic chicken embryo, both c-AMP and GMP concentrations were decreasing in the pectoral muscles in parallel with the advancement of hatching stages.

Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency

“…Sildenafil also significantly reduces exerciseinduced ischemia (33), a potentially important pathogenetic mechanism in dystrophin-deficient skeletal muscle (10,34). In fact, defects in cGMP signaling are also suggested from studies in dystrophin-deficient skeletal muscle (35,36), and recently, Asai et al (37) showed that treatment with tadalafil, another known PDE5 inhibitor, ameliorates contraction-induced skeletal muscle damage. Finally, sildenafil can cross the blood-brain barrier to inhibit brain PDE5A (38), which could theoretically affect sympathetic and parasympathetic outflow.…”