Hyperbaric oxygen increases the lung's susceptibility to inhaled lipopolysaccharide in mice.

Hyperbaric oxygen (HBO2) has been shown to inhibit the adhesion function of beta(2)-integrin, which is important in mediating cell-to-cell adhesion and extravasation of inflammatory cells. In the present study, we examined the effects of HBO2 exposure on neutrophil infiltration and tissue injury in a model of acute lung inflammation induced by lipopolysaccharide (LPS) inhalation. Male C57BL/6 mice of 8 weeks old were exposed to 3 atmosphere absolute (ATA) 100% HBO2, 3 ATA hyperbaric air (HBA), or room air for 90 min. After exposure, they were exposed to aerosolized LPS solution (1 mg/ml) or saline in a plexiglass chamber for 10 min. Four hours after inhalation, bronchoalveolar lavage (BAL) was performed to determine protein concentration, LDH activity, total cells, and differential cell counts in the lavage fluid (BALF). Myeloperoxidase (MPO) content, lung histopathology, and plasma nitric oxide (NO) metabolite concentrations were also determined in separate sets of animals. We observed that LPS inhalation increased neutrophil number in the BALF, which was significantly inhibited by HBO2 but not HBA pre-exposure. However, MPO content in the lung was prominently increased by HBO2 pre-exposure, which correlated with increased PMN infiltration in lung tissues. Further, HBO2 plus LPS, but not saline inhalation caused a significant increase in the BALF protein level and LDH activity compared with that of LPS inhalation alone. LPS exposure induced significant increase in plasma NO metabolites, which was not potentiated by HBO2 pre-exposure. The inducible nitric oxide synthase inhibitor, aminoguanidine, significantly attenuated the increases in plasma NO metabolites and tissue MPO content as well as lung injuries. In summary, our data suggest that HBO2 pre-exposure increases the lung's susceptibility to inhaled LPS, which may be related to increased tissue neutrophil infiltration and dependent on interaction(s) between HBO2 exposure with LPS-induced nitric oxide production.

D-amphetamine-induced depletion of energy and dopamine in the rat striatum is attenuated by nicotinamide pretreatment.

The present study examined the effects of nicotinamide on the D-amphetamine (AMPH)-induced dopamine (DA) depletion and energy metabolism change in the rat striatum. In chronic studies, co-administration of AMPH with desipramine, a drug that retards the metabolism of AMPH, (10 mg/kg, intraperitoneal [i.p.], respectively) caused a significant decrease of striatal DA content measured 7 days later. Pretreatment with nicotinamide (500 mg/kg, i.p.), the precursor molecule for the electron carrier molecule nicotinamide adenine dinucleotide (NAD), attenuated this effect of AMPH, whereas itself exerted no long-term effect on striatal DA content. In acute studies, a decrease in striatal adenosine triphospate/adenosine diphosphate (ATP/ADP) ratio was found 3 h after co-injection of AMPH and desipramine. However, nicotinamide pretreatment blocked the reduced striatal ATP/ADP ratio and resulted in a striking increase in striatal NAD content in AMPH-treated rats. Furthermore, nicotinamide was noted to increase striatal ATP/ADP ratio and NAD content in saline-treated rats. These findings suggest that nicotinamide protects against AMPH-induced DAergic neurotoxicity in the striatum of rats via energy supplement.

Ionic mechanisms of tetrandrine in cultured rat aortic smooth muscle cells.

The ionic mechanism of tetrandrine, an alkaloid extracted from the Chinese medicinal herb Radix stephania tetrandrae, was investigated in A7r5 vascular smooth muscle cells. The nystatin-perforated whole-cell voltage-clamp technique was performed to examine the effects of tetrandrine on ionic currents. Tetrandrine (1-100 microM) reversibly caused an inhibition of L-type voltage-dependent Ca2+ current (I(Ca,L)) in a concentration-dependent manner. Tetrandrine did not cause any change in the overall shape of the current-voltage relationship of I(Ca,L). The IC50 value of tetrandrine-induced inhibition of I(Ca,L) was 5 microM. In the presence of Bay K 8644 (3 microM) or cyclopiazonic acid (30 microM), tetrandrine still produced a significant inhibition of I(Ca,L). The inhibitory effects of tetrandrine on I(Ca,L) exhibited tonic and use-dependent characteristics. Moreover. tetrandrine (3 microM) shifted the steady-state inactivation curve of I(Ca,L) to more negative membrane potentials by approximately -15 mV. These results indicate that tetrandrine directly inhibits the voltage-dependent L-type Ca2+ current in vascular smooth muscle cells, which may predominantly contribute to the vasodilatory actions of tetrandrine.

Effects of acute and chronic morphine on DOPAC and glutamate at subcortical DA terminals in awake rats.

Effects of morphine and naloxone on the levels of 3,4-dihydroxy-phenylacetic acid (DOPAC) and glutamate in the striatum and nucleus accumbens of awake rats were studied with in vivo microdialysis. Acute morphine (50 mg/kg, IP) treatment increased the levels of DOPAC and glutamate in the striatum and nucleus accumbens, but both decreased from the elevated levels when naloxone (10 mg/kg, IP) was given 2 h later. Chronic morphine treatment, twice daily for 5 days in incremental doses (5, 10, 20, 40 and 50 mg/kg, IP), increased the level of DOPAC but decreased that of glutamate in the striatum and nucleus accumbens. When naloxone was given 2 h later, the reverse of the above phenomena are found. After given repeated morphine treatment and experiencing naloxone-precipitated withdrawal, the rats with an intact cortex and the rats with ibotenic acid (5 microg/0.5 microl/2.5 min) lesions on the medial prefrontal cortex and sulcal cortex have similar alternations in the levels of DOPAC and glutamate in the striatum. However, in the nucleus accumbens, the level of DOPAC dropped more and the level of glutamate increased more in the intact rats than the lesioned rats during the withdrawal stage. These data suggested that the intact cortex ordinarily exerted an inhibitory role to influence the level of DOPAC in the striatum and nucleus accumbens during chronic morphine treatment. In conclusion, morphine seems to activate different pathways in dependent and non-dependent rats.

Adenosine and glutamate modulate the cardiovascular responses of angiotensins II and III in the area postrema of rats.

The purpose of this study was to determine the interactions of the renin-angiotensin system with adenosine and glutamate in the area postrema (AP) of rats. Male Sprague-Dawley rats were anesthetized with urethane. Adenosine, angiotensins (Ang) II, III and their antagonist 1,3-Dipropyl-8-p-sulfophenylxanthine (DPSPX), [Sar1Ile7]Ang III and glutamate antagonist, L-glutamic acid diethyl ester (GDEE) were microinjected into the AP of rats. Our results demonstrated that microinjection of DPSPX significantly attenuated the depressor and bradycardic effects of Ang II and III at low (9.6 pmol) and high dose (480 pmol) of Ang II in normotensive rats. To test the interaction of glutamate and renin-angiotensin system, we found that glutamate antagonist, GDEE, markedly lowered depressor and bradycardic responses of Ang II but did not influence Ang III in rats. On the other hand, microinjection of the Ang antagonist [Sar1Ile7]Ang III 10 min prior to the injection of adenosine significantly altered the cardiovascular effects of adenosine in the AP. In conclusion, the endogenous adenosine and glutamate may influence the renin-angiotensin system on cardiovascular responses in the AP of rats.

The role of atrial natriuretic factor in dehydration and schedule-induced drinking behaviour.

Dehydration-induced drinking (DID) has been defined as a type of homeostatic behaviour controlled by factors related to water balance, whereas schedule-induced polydipsia (SIP) is considered to be a type of nonhomeostatic drinking subsequent to a general increase in motor excitability. In this study, we have attempted to assess the role of atrial natriuretic factor (ANF) in both models to elucidate the mechanisms controlling water intake. Intracerebroventricular injection of ANF (2-8 nmol) caused a dose related suppression of water intake in both DID and SIP, but intravenous injection with a higher dose of ANF (8 nmol) produced a significant suppression of water intake only in DID. Before drinking started, tissue ANF levels increased in atria in both models and decreased in hypothalamus in DID but not in SIP. After 1 hour of drinking, ANF levels decreased in atria in both models and increased in hypothalamus in SIP but not in DID. These results suggest that DID and SIP are different in their thirst regulation, and that the notion that peripheral ANF serves as a humoral factor sending signals to central in the fluid homeostatic control mechanism is questionable.