Activation of noradrenergic mechanism attenuates glutamate-induced vasopressor responses in the pons and medulla of cats in vivo.

1. Using anesthetized cats, the authors examined the noradrenergic modulation of the glutamate induced pressor and depressor responses in various brainstem areas, including pontine gigantocellular tegmental field (FTG), dorsomedial medulla (DM), rostral ventrolateral medulla (RVLM), and caudal ventrolateral medulla (CVLM). 2. Unilateral microinjection of L-glutamate (Glu, 3 nmol in 30 nL saline) into FTG, DM and RVLM produced an increase in systemic arterial pressure (SAP) and a decrease in heart rate (HR), while into CVLM produced decreases of SAP and HR. 3. Application of norepinephrine (NE) into the pressor areas (0.05 to 5 nmol) did not alter the resting SAP and HR, but significantly attenuated the Glu-induced pressor response with an order of potency: FTG > DM > RVLM. In the depressor CVLM, NE alone produced a dose-dependent decrease of resting SAP and HR, but did not affect the Glu-induced depressor responses. 4. The involvement of different adrenoceptor subtypes was further investigated by application of selective adrenoceptor agonists including phenylephrine (alpha1), clonidine (alpha2), and isoproterenol (beta). Responses to these agonists are similar to those elicited by NE, except that only alpha-adrenoceptor agonists could antagonize the Glu-induced pressor responses of the RVLM. 5. Our observations indicate that NE not only inhibits the pressor mechanisms in various brainstem areas but also elicits a direct depressor response in CVLM. These findings also suggest that NE acts more likely a neurotransmitter, rather than a modulator, in the CVLM.

Role of nitric oxide on pressor mechanisms within the dorsomedial and rostral ventrolateral medulla in anaesthetized cats.

1. The role of nitric oxide (NO) in central cardiovascular regulation and the correlation between NO and glutamate-induced mechanisms is not clear. Microinjection of glutamate (3 nmol/30 nL) into dorsomedial medulla (DM) and rostral ventrolateral medulla (RVLM) increased arterial blood pressure (BP) and sympathetic vertebral nerve activity (VNA). Thus, in the present study, we examined the modulation by NO of glutamate-induced pressor responses in the DM and RVLM of cats. 2. Histochemical methods using nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) as a marker to stain neurons containing NO synthase (NOS), showed positive findings of NOS in both the DM and RVLM. 3. Microinjection of N(G)-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, into the DM or RVLM did not alter resting BP and VNA, but it did cause a dose-dependent attenuation of glutamate-induced pressor responses. Interestingly, the increase in NO levels that resulted from pretreatment with L-arginine (L-Arg) or sodium nitroprusside (SNP) did not alter resting BP and VNA, but still inhibited glutamate-induced pressor responses in the DM and RVLM in a dose-dependent manner. 4. We also examined whether NO modulated the pressor responses induced by activation of different excitatory amino acid receptors. N-Methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) were used. Consistent with the results from the initial glutamate studies, we observed that not only L-NAME, but also L-Arg and SNP attenuated pressor responses induced by NMDA and AMPA. No difference was found between the effects of NO on NMDA- and AMPA-induced pressor responses. 5. To investigate the possibility of a loss of agonist selectivity, the effects of D-2-amino-5-phosphonovalerate (D-AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on AMPA and NMDA responses in the DM were examined. The results showed that CNQX did not alter NMDA-induced pressor responses, while D-AP5 failed to alter AMPA-induced responses. 6. Our results suggest that activation of the glutamate-induced pressor mechanism is regulated by changes in NO levels in the DM and RVLM. This implies that NO may play a permissive role to allow operation of the glutamate-activation mechanism.

Prolonged exposure to hyperbaric oxygen induces neuronal damage in primary rat cortical cultures.

While seizure attack is one of the serious complications during the hyperbaric oxygen (HBO) therapy, there is still no direct evidence showing that HBO can induce neuronal damage in the brain. The objective of this study was first to investigate whether HBO would lead to neurotoxicity in the primary rat cortical culture. Second, since alterations in neurotransmitters have been suggested in the pathophysiology of central nervous system (CNS) oxygen toxicity, the protective effects of the N-methyl-D-aspartate (NMDA) receptor antagonism and nitric oxide (NO) synthase inhibition on the HBO-induced neuronal damage were examined. The results showed that HBO exposure to 6 atmosphere absolute pressure (ATA) for 30, 60, and 90 min increased the lactate dehydrogenase (LDH) activity in the culture medium in a time-dependent manner. Accordingly, the cell survival, measured by the 3,(4,5-dimethyl-2-thiazolyl)2, 5-diphenyl-tetrazolium bromide (MTT) assay, was decreased after HBO exposure. Pretreatment with the NMDA antagonist MK-801 protected the cells against the HBO-induced damage. The protective effect was also noted in the cells pretreated with L-N(G)-nitro-arginine methyl ester, an NO synthase inhibitor. Thus, our results suggest that activation of NMDA receptors and production of NO play a role in the neurotoxicity produced by hyperbaric oxygen exposure.

Systemic administration of D-amphetamine induced a delayed production of nitric oxide in the striatum of rats.

Nitric oxide (NO) is a free-radical gas with a role in various signal transduction processes. In the CNS, NO acts as an important central nervous messenger, but in excess it may be neurotoxic. Chronic or high dose administration of D-amphetamine (AMPH) has been shown to induce striatal neurotoxicity in rodents and primates. In this study, we studied whether AMPH given systemically elicits NO formation in the striatum of rats and determined the relationship between NO formation and striatal DAergic terminal damage. Our results demonstrated that a single large dose administration of AMPH with desipramine elicited a delayed production of NO and concomitant long-term DA loss in the striatum. These phenomena were blocked by treatment with either the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) or the glutamate N-methyl-D-aspartate antagonist MK-801. It appears that AMPH-induced NO formation is critical for development of long-lasting DAergic terminal toxicity in the striatum of rats.

Precollicular decerebration reduces the pressor responses evoked by stimulation of rostral pons but not medulla in cats.

In 30 cats under chloralose (40 mg/kg) and urethane (400 mg/kg) anesthesia, the ponto-medullary region involved in cardiovascular integration were stimulated by rectangular pulses (0.5 ms, 80 or 5 Hz, 100 to 200 microA) and/or by microinjection of sodium glutamate (Glu, 0.25-0.5 M, 70-200 nl). Changes of systemic arterial blood pressure (SAP) and renal sympathetic nerve activity (RNA) following stimulation were compared before and after precollicular decerebration. Precollicular decerebration itself resulted in an immediate but brief (5 to 15 min) hypotension with a decrease in SAP ranging from 40 to 100 mmHg. Stimulation of the lateral tegmental field (FTL) produced depressor responses. After precollicular decerebration, the stimulation induced depressor responses were either abolished or converted to mild pressor responses. Stimulation of the dorsal gigantocellular tegmental field-periventricular grey (dFTG-PVG) produced pressor responses. These responses were abolished after precollicular decerebration without exception. On the other hand, precollicular decerebration did not reduce pressor responses produced by stimulation of the ventrolateral medulla (VLM) and the dorsal medulla (DM). In 7 additional cats killed with an overdose of pentobarbital, the brain stem were processed for dopamine beta-hydroxylase (DBH). The pressor areas of the VLM and DM were DBH positive, indicating the presence of norepinephrine, while the dFTG-PVG and FTL were not. These findings suggest that the depressor mechanism of the FTL and the pressor mechanism of the dFTG, but not of the VLM or DM depend on actions of the brain structures rostral to superior colliculi.

Protozoan and helminth parasites of humans in mainland China.

To date, 30 species of protozoa, 12 species of cestodes, 26 species of trematodes, 23 species of nematodes, two species of gordius and one acanthocephalan species hae been reported as parasites of man in mainland China.

Comparison of morphology, pathogenicity and drug response among three isolates of Schistosoma japonicum in the mainland of China.

Geographic differences among isolates of Schistosoma japonicum from Anhui Province (A) in the east, Guangxi Autonomous Region (G) in the south and Yunnan Province (Y) in the southwest of mainland of China were studied. C57BL mice were used to compare these isolates. Morphologically, both male and female worms of isolate Y were shorter than those of isolates A and G, and the ovary of female worm of isolate G was the smallest. In isolate A, the percentage of male worms bearing 7 testes was 87%, while 64% of isolate Y and 75% of isolate G were with 7 testes. As to the volume of hepatic egg granuloma which was used as a parameter of pathogenicity in our experiment, that of isolate G was the smallest. The sensitivity to praziquantel of isolates was estimated by parasite reduction rate at ED50 (230 mg/kg) level. It was found that isolate Y's response was significantly higher than that of isolates A and G, and the latter two were similar in drug response. The results indicate significant differences among the three isolates studied.

Schistosomiasis control in the people's Republic of China.

Evidence exists that schitosomiasis japonica has been present in China for more than 2,200 years. The first parasitologically confirmed clinical case was reported in 1905. Fragmentary surveys before 1949 suggested that there were 5 million schistosomiasis patients distributed in 138 hsiens (counties); however, a more systematic survey after the founding of the People's Republic showed that these figures represented only 50% of patients and 40% of infected hsiens. Based on the epidemiological pattern and ecological characteristics of the snail intermediate host, endemic areas have been divided into three strata: plain region, mountainous and hill region, and marshland and lake region. Following comprehensive control measures, with stress on applied research and integrating technical work with involvement of the population, in 204 hsiens the snail control programs are now considered to be relatively consolidated and the number of patients needing treatment is relatively few. In the marshland and lake region and mountainous region eradication of schistosomiasis remains a difficult problem.