We investigated whether low-level laser therapy (LLLT) can reduce muscular fatigue during tetanic contractions in rats. Thirty-two male Wistar rats were divided into four groups receiving either one of three different LLLT doses (0.5, 1.0, and 2.5 J/cm2) or a no-treatment control group. Electrical stimulation was used to induce six tetanic muscle contractions in the tibial anterior muscle. Contractions were stopped when the muscle force fell to 50% of the initial value for each contraction (T50%). There was no significant difference between the 2.5 J/cm2 laser-irradiated group and the control group in mean T50% values. Laser-irradiated groups (0.5 and 1.0 J/cm2) had significantly longer T50% values than the control group. The relative peak force for the sixth contraction in the laser-irradiated groups were significantly higher at 92.2% (SD 12.6) for 0.5 J/cm2, 83.2% (SD 20.5) for 1.0 J/cm2, and 82.9% (SD 18.3) for 2.5 J/cm2 than for the control group [50% (SD 15)]. Laser groups receiving 0.5 and 1.0 J/cm2 showed significant increases in mean performed work compared with both the control group and their first contraction values. Muscle damage was indirectly measured by creatine kinase levels in plasma. A distinct dose-response pattern was found in which 1.0 and 2.5 J/cm2 LLLT groups had significantly lower creatine kinase levels than the 0.5 J/cm2 LLLT group and the control group. We conclude that LLLT doses of 0.5 and 1.0 J/cm2 can prevent development of muscular fatigue in rats during repeated tetanic contractions.

Nitric oxide is a crucial mediator of gastrointestinal mucosal defense, but, paradoxically, it also contributes to mucosal injury in several situations. Inhibitors of nitric oxide synthesis and compounds that release nitric oxide have been useful pharmacological tools for evaluating the role of nitric oxide in gastrointestinal physiology and pathophysiology. Newer inhibitors with selectivity for one of the isoforms of nitric oxide synthase are even more powerful tools and may have utility as therapeutic agents. Also, agents that can scavenge nitric oxide or peroxynitrite are promising as drugs to prevent nitric oxide-associated tissue injury. Compounds that release nitric oxide in small amounts over a prolonged period of time may also be very useful for prevention of gastrointestinal injury associated with shock and with the use of drugs that have ulcerogenic effects. Indeed, the coupling of a nitric oxide-releasing moiety to nonsteroidal anti-inflammatory drugs has proven to be a valid means of substantially reducing the gastrointestinal toxicity of these drugs without decreasing their efficacy.

1 Selective inhibitors of cyclo-oxygenase-2 have been shown to be e ective anti-in¯ammatory drugs with reduced gastrointestinal toxicity relative to conventional nonsteroidal anti-in¯ammatory drugs (NSAIDs). In the present study, we examined the possibility that selective COX-2 inhibition, by blocking prostacyclin synthesis, would increase blood pressure and cause leukocyte adherence and platelet aggregation. 2 Normal rats and rats with hypertension induced by chronic administration of N o -nitro-Larginine methylester were given celecoxib (10 mg kg 71 ) daily for 3 weeks. Celecoxib signi®cantly elevated of blood pressure in both the normal and hypertensive rats (mean increase of 433 mm Hg after 3 weeks). 3 In normal rats, celecoxib had no e ect on serum 6-keto prostaglandin (PG)F 1a levels. Hypertensive rats exhibited a signi®cant increase (82%) in serum 6-keto PGF 1a levels, and this was reduced to the levels of normal rats by treatment with celecoxib. 4 Rats treated with celecoxib exhibited signi®cant increases in weight gain (20%), plasma argininevasopressin levels (148%) and plasma urea (69%) relative to vehicle-treated controls. Plasma creatinine levels were una ected by treatment with celecoxib, while plasma renin levels were signi®cantly decreased (30%) relative to controls. 5 Superfusion of mesenteric venules with celecoxib (3 mM) in vivo resulted in signi®cant increases in leukocyte adherence to the endothelium in both normal and hypertensive rats. 6 These studies suggest that suppression of COX-2 signi®cantly in¯uences vascular and/or renal function, leading to elevated blood pressure and leukocyte adherence.

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1 Selective cyclo-oxygenase (COX)-2 inhibitors and nitric oxide-releasing nonsteroidal antiin¯ammatory drugs (NSAIDs) exhibit reduced toxicity in the gastrointestinal tract, but may a ect wound healing in other tissues. In this study, we have compared the e ects of a selective COX-2 inhibitor (celecoxib), a nitric-oxide releasing derivative of naproxen (HCT-3012) and naproxen in a model of wound collagen deposition in the rat. 2 Polyvinyl alcohol sponges were implanted subcutaneously in rats. The rats were treated daily for 5 days with the test drugs at equie ective anti-in¯ammatory doses. 3 Naproxen (10 mg kg 71 ) signi®cantly decreased (45%) collagen deposition at the wound site relative to the vehicle-treated control group. In contrast, HCT-3012 (14.5 mg kg 71 ) signi®cantly increased (62%) collagen deposition, while celecoxib (10 mg kg 71 ) had no e ect. 4 Naproxen and HCT-3012 suppressed prostaglandin (PG) E 2 levels at the wound site and whole blood thromboxane synthesis to similar degrees. Celecoxib had no signi®cant e ect on wound¯uid PGE 2 levels, but slightly reduced whole blood thromboxane synthesis (by 17%). 5 COX-1 mRNA and protein were expressed in the wound exudate, the skin surrounding the wound and in normal skin. In contrast, COX-2 mRNA, but not protein, was expressed in wound and normal skin. 6 These results demonstrate that HCT-3012 can signi®cantly enhance collagen deposition at a wound site, despite inhibiting prostaglandin synthesis to the same extent as the parent drug. Nitric oxide-releasing NSAIDs may represent a safer alternative to standard NSAIDs for use as antiin¯ammatory and analgesic agents by post-surgery patients.