Microcirculatory effects of melatonin in rat skeletal muscle after prolonged ischemia

Abstract

The purpose of this study was to determine microcirculatory effects and response of nitric oxide synthase (NOS) to melatonin in skeletal muscle after prolonged ischemia. A vascular pedicle isolated rat cremaster muscle model was used. Each muscle underwent 4 hr of zero-flow warm ischemia followed by 2 hr of reperfusion. Melatonin (10 mg/kg) or saline as a vehicle was given by intraperitoneal injection at 30 min prior to reperfusion and the same dose was given immediately after reperfusion. After reperfusion, microcirculation measurements including arteriole diameter, capillary perfusion and endothelial-dependent and -independent vasodilatation were performed. The cremaster muscle was then harvested to measure endothelial NOS (eNOS) and inducible NOS (iNOS) gene expression and enzyme activity. Three groups of rats were used: sham-ischemia/reperfusion (I/R), vehicle + I/R and melatonin + I/R. As compared with vehicle + I/R group, administration of melatonin significantly enhanced arteriole diameter, improved capillary perfusion, and attenuated endothelial dysfunction in the microcirculation of skeletal muscle after 4 hr warm ischemia. Prolonged warm ischemia followed by reperfusion significantly depressed eNOS gene expression and constitutive NOS activity and enhanced iNOS gene expression. Administration of melatonin did not significantly alter NOS gene expression or activity in skeletal muscle after prolonged ischemia and reperfusion. Melatonin provided a significant microvascular protection from reperfusion injury in skeletal muscle. This protection is probably attributable to the free radical scavenging effect of melatonin, but not to its anti-inflammatory effect.

Melatonin Prevents Cyclosporine-Induced Hepatotoxicity in Rats

“…Recent data suggest that oxidative stress is the underlying mechanism of CsA-related apoptosis [1,[14][15][16][17] . Melatonin, the chief indolamine secreted from the pineal gland, is an effective antioxidant agent [2,4,18] . Antioxidant agents operate through neutralizing the toxic reactants, and reducing the molecular damage to the free radicals [2,19] .…”

Effects of supplementation of BH4 after prolonged ischemia in skeletal muscle

“…Muscle Model [27][28][29][30] Briefly, an incision was made on the ventral aspect of the animal from the anterior iliac spine to the tip of the scrotum. Under observation with a stereomicroscope, the connective tissue of the scrotal sac was removed from around the cremaster muscle by careful blunt dissection.…”

Melatonin Regulates Nitric Oxide Synthase Expression in Ischemic Brain Injury

“…Our results showed that eNOS levels decline in MCAO-induced brain injury, and melatonin prevents decrease of eNOS levels. Melatonin provides a significant microvascular protection through the activation of eNOS [23]. Moreover, melatonin-induced protection involves vascular mechanism through the vasodilatation after cerebral ischemia [9].…”