nitroarginine and Fever

The possible involvement of nitric oxide (NO) in morphine-induced catalepsy and hyperthermia was studied in morphine-dependent rats. Four days repeated injection regimen was used to induce morphine dependence, which was assessed by naloxone challenge (0.5 mg x kg(-1), s.c.). Pretreatment of rats with the NO synthase inhibitor, N(G)-nitro-L-arginine (L-NA, 8 mg x kg(-1) twice daily, i.p.) potentiated the cataleptic response of morphine as shown by a rightward shift in the morphine-log dose-response curve. Prior treatment of rats with the NO precursor, L-arginine (200 mg x kg(-1), twice daily, i.p.) abolished the potent effect of L-NA and restored the cataleptic scores to levels similar to those of morphine-dependent rats. The same dose of L-NA significantly blocked morphine-induced hyperthermia at the dose levels of morphine (15-105 mg x kg(-1)) and this effect was reversed by L-arginine. These data provide the first experimental evidence that NO is involved in morphine induced catalepsy and hyperthermia and demonstrated that blockade of NO synthesis may suggest a dangerous interaction with opioids in the control of motor function.

Topics: Animals; Arginine; Catalepsy; Enzyme Inhibitors; Fever; Male; Morphine; Morphine Dependence; Naloxone; Narcotic Antagonists; Narcotics; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Rats; Substance Withdrawal Syndrome

Nitric oxide (NO) is one of the most important biologic messengers and takes part in the development of fever. It can influence on the body prooxidant-antioxidant balance by different ways including interaction with hemoglobin (Hb).. The effects of nitric oxide synthesis inhibition on the febrile response, hemoglobin-oxygen affinity and parameters of lipid peroxidation were studied in rabbits with fever. The fever was induced by intravenous administration of lipopolysaccharide from Salmonella typhi (0.6 microg/kg). Mixed venous blood was taken before the administration and 60, 120 and 180 min after it. The following parameters were measured: half-saturation oxygen pressure (P(50)), concentrations of conjugated dienes, Schiff bases and alpha-tocopherol in plasma and red blood cells, and activity of catalase in red blood cells.. The intravenous administration of the nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine; 5x10(-3) M) reduced the lipopolysaccharide-induced rise in body temperature. After 180 min the actual P(50) had decreased from 35.0+/-1.7 to 29.4+/-1.3 mm Hg. An increase in the lipid peroxidation parameters and a decrease of the antioxidant system indices were observed. The administration of L-arginine to prevent nitric oxide synthase inhibition was accompanied by a shift of the oxyhemoglobin dissociation curve rightwards, more marked activation of the free radical processes and a greater elevation of body temperature. The multiple regression analysis showed a close linear correlation between P(50) and conjugated dienes, Schiff bases, alpha-tocopherol and catalase.. These results suggest that the increased hemoglobin-oxygen affinity found after the inhibition of nitric oxide synthesis lowers the oxygen flow to tissues and its fraction utilized in free radical oxidations, which finally causes a reduction of the fever response to the lipopolysaccharide.

Topics: Animals; Enzyme Inhibitors; Fever; Lipid Peroxidation; Lipopolysaccharides; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Oxyhemoglobins; Rabbits

Hypoxia causes a regulated decrease in body temperature (T(b)), and nitric oxide (NO) is now known to participate in hypoxia-induced hypothermia. Hypoxia also inhibits lipopolysaccharide (LPS)-induced fever. We tested the hypothesis that NO may participate in the hypoxia inhibition of fever. The rectal temperature of awake, unrestrained rats was measured before and after injection of LPS, with or without concomitant exposure to hypoxia, in an experimental group treated with N(omega)-nitro-L-arginine (L-NNA) for 4 consecutive days before the experiment and in a saline-treated group (control). L-NNA is a nonspecific NO synthase inhibitor that blocks NO production. LPS caused a dose-dependent typical biphasic rise in T(b) that was completely prevented by hypoxia (7% inspired oxygen). L-NNA caused a significant drop in T(b) during days 2-4 of treatment. When LPS was injected into L-NNA-treated rats, inhibition of fever was observed. Moreover, the effect of hypoxia during fever was significantly reduced. The data indicate that the NO pathway plays a role in hypoxia inhibition of fever.

Topics: Animals; Body Temperature; Enzyme Inhibitors; Fever; Hypoxia; Lipopolysaccharides; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Rats; Rats, Wistar

To analyze the effect of hyperthermia on the vascular response, the isometric response of isolated rabbit femoral artery segments was recorded at 37 degreesC and hyperthermia (41 and 44 degreesC). Contraction to potassium (5 x 10(-3)-5 x 10(-2) M) was significantly greater at 41 and 44 than at 37 degreesC and increased by inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine (L-NNA; 10(-4) M) or endothelium removal at 37 degreesC but not at 41 or 44 degreesC. Norepinephrine (10(-9)-10(-4) M) produced a concentration-dependent contraction greater at 41 or 44 than at 37 degreesC and not modified by endothelium removal or L-NNA at either temperature. Phenylephrine (10(-9)-10(-4) M) produced a contraction increased by warming to 44 degreesC but not to 41 degreesC. The specific alpha2-adrenoceptor agonist BHT-920 produced a weak contraction, reduced by the alpha1-adrenoceptor antagonist prazosin (10(-6) M) and increased at 44 degreesC but not at 41 degreesC. The concentration-dependent contraction to endothelin-1 (ET-1; 10(-11)-10(-7) M) was increased by warming to 41 and 44 degreesC and by endothelium removal or L-NNA at 37 degreesC but not at 41 or 44 degreesC. Response to ET-1 was reduced by endothelin ETA-receptor antagonist BQ-123 (10(-5) M) and ETB-receptor antagonist BQ-788 (10(-5) M). In arteries precontracted with ET-1 (10(-8)-3 x 10(-8) M), relaxation to sodium nitroprusside (10(-8)-10(-4) M) was increased at 41 and 44 degreesC vs. at 37 degreesC, but that of ACh (10(-8)-10(-4) M) or adenosine (10(-8)-10(-4) M) was not different at all temperatures studied. Relaxation to ACh, but not adenosine, was reduced similarly by L-NNA at all temperatures studied. These results suggest hyperthermia in muscular arteries may inhibit production of, and increase dilatation to, NO, resulting in unchanged relaxation to ACh and increased constriction to KCl and ET-1, and may increase constriction to stimulation of alpha1-adrenoceptors by NO-independent mechanisms.

Topics: Acetylcholine; Adenosine; Animals; Azepines; Endothelin Receptor Antagonists; Endothelin-1; Femoral Artery; Fever; In Vitro Techniques; Nitric Oxide; Nitroarginine; Nitroprusside; Norepinephrine; Potassium Chloride; Rabbits; Receptors, Adrenergic, alpha; Vasoconstriction; Vasodilation

I.v. administration of NG-nitro-L-arginine attenuated a fever response in rabbit. Preliminary administration of L-arginine for prevention of the NO-synthase inhibition suppressed the blood oxygen transport function and augmented the fever response.

Topics: Animals; Enzyme Inhibitors; Fever; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Oxygen; Rabbits

1. This study investigates the effects of the nitric oxide donors on lipopolysaccharide-induced fever in rabbits, and the effect of brain nitric oxide synthase inhibition on the febrile response in pyrogen tolerant animals. 2. The febrile response was reduced by intravenous injections of the nitric oxide donors molsidomine (1.0 mg/kg) and isosorbide dinitrate (0.5 mg/kg) 60 min after intravenous treatment with lipopolysaccharide. 3. The magnitude of fever was also attenuated by intracerebroventricular administration of molsidomine (75 micrograms). 4. Intracerebroventricular pretreatment with the nitric oxide synthase inhibitor, NG-nitro-L-arginine (100 micrograms) 10 min before the injection of lipopolysaccharide significantly enhanced the febrile response in pyrogen tolerant animals. 5. The results suggest that nitric oxide is involved in the central mechanisms of thermoregulation during fever as one of the effective endogenous antipyretics.

Topics: Amino Acid Oxidoreductases; Animals; Arginine; Body Temperature Regulation; Brain; Fever; Injections, Intraventricular; Isosorbide Dinitrate; Lipopolysaccharides; Male; Molsidomine; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Rabbits; Salmonella typhi

We have shown previously that an increase in ear blood flow velocity (EBF) in the conscious, chronically instrumented rabbit during whole body heating (WBH) involves active neurogenic vasodilation that is abolished by local nerve block. This study was designed to test the potential role of nitric oxide (NO) in rabbit ear neurogenic vasodilation during hyperthermia. Rabbits were instrumented for the measurement of arterial pressure, heart rate, and EBF (Doppler ultrasound). A catheter was also placed in the left lingual artery for administration of drugs to the left ear. WBH was achieved by circulating warm water through a rubber pad placed around the rabbit. Internal temperature was measured with a rectal thermocouple. During WBH, bolus injections of N omega-nitro-L-arginine (L-NNA), a false substrate for the formation of NO, were given via the lingual artery (10(-5) M, 4-5 ml total) to determine whether NO was involved in the increase in EBF. During WBH, left ear vascular conductance (EVC) increased from 0.07 +/- 0.03 to 5.87 +/- 0.73 kHz/100 mmHg and right EVC from 0.20 +/- 0.13 to 4.49 +/- 1.73 kHz/100 mmHg. When EVC was maximum, L-NNA was administered into the left lingual artery. EVC began to decrease after a latency of 23 min. At 56 +/- 8 min, left and right EVC had decreased to 0.18 +/- 0.10 and 0.23 +/- 0.11 kHz/100 mmHg, respectively (P < 0.05). Subsequent infusions of L-arginine, the true substrate for NO formation, restored EVC. These results suggest that NO is involved in active vasodilation during heating in the rabbit ear.

Topics: Acetylcholine; Animals; Arginine; Blood Pressure; Body Temperature Regulation; Ear; Fever; Nitric Oxide; Nitroarginine; Rabbits; Regional Blood Flow; Vasodilation