Biomedical subjects

F Zhang

Publications and source records attributed to F Zhang.

At least 559 records · Page 31Linked to original sources

PubMed1994

17 beta-Estradiol attenuates voltage-dependent Ca2+ currents in A7r5 vascular smooth muscle cell line.

Previous studies have shown that 17 beta-estradiol (beta-E2) has a direct acute inhibitory effect on vascular smooth muscle (VSM) contraction. To investigate the mechanisms underlying this phenomenon, we utilized whole cell patch-clamping techniques to study effects of beta-E2 on voltage-dependent Ca2+ channels in cultured VSM cells (VSMC). T- and L-type Ca2+ currents were characterized with ramp and pulse protocols in A7r5 cultured VSMC. T-type current, inactivated in < 100 ms, was reduced by Ba2+ and was comparatively little affected by isradipine. L-type current required higher voltages to activate, inactivated slowly, was greatly increased by Ba2+, and could be completely inhibited by 5 microM isradipine. beta-E2 (10 microM) significantly reduced peak L-type Ba2+ current and T-type Ca2+ current within 1-2 min, whereas alpha E2 (a hormonally inactive isomer of estradiol) caused significantly less reduction in both types of current. Vehicle (0.1% ethanol) had no significant effect on either current. The inhibitory effect of beta-E2 on voltage-dependent Ca2+ currents may contribute to previously demonstrated beta-E2 attenuation of VSM contraction.

Animals↗

PubMed1994

Nitric oxide-dependent and -independent components of cerebrovasodilation elicited by hypercapnia.

We studied the effect of nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on the increases in cerebral blood flow (CBF) elicited by stepwise elevations in arterial partial pressure of CO2 (PaCO2) from normocapnia up to 204 mmHg. Rats were anesthetized with halothane and ventilated. CBF was monitored over the parietal cortex using a laser-Doppler flowmeter. Increasing levels of hypercapnia elicited graded elevations in CBF that reached a plateau at PaCO2 = 82 +/- 1 mmHg (CBF +215 +/- 25%; n = 8; P < 0.05, analysis of variance). L-NAME (40 mg/kg i.v.; n = 8), but not nitro-D-arginine methyl ester (n = 8), reduced resting CBF (-42 +/- 4%) and attenuated the increase in CBF elicited by hypercapnia. The attenuation occurred only at PaCO2 40-80 mmHg and was maximal (-75 +/- 8%; P < 0.05) at 54 +/- 2 mmHg. At PaCO2 > or = 100 mmHg, L-NAME (40-80 mg/kg) did not attenuate the response (P > 0.05). Reduction of resting CBF (-50 +/- 4%; n = 6) by administration of chloralose (20-40 mg/kg i.v.) did not attenuate the CBF response to hypercapnia (P > 0.05). We also found that the attenuation by L-NAME of resting CBF (n = 5) and of the cerebrovasodilation elicited by hypercapnia (n = 6) has a relatively slow time course, the effects reaching a maximum 45-60 min after intravenous administration of the drug. We conclude that L-NAME does not attenuate the CBF response to CO2 uniformly at all levels of hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMed1994

SIN-1 reverses attenuation of hypercapnic cerebrovasodilation by nitric oxide synthase inhibitors.

We sought to determine whether the attenuation of the hypercapnic cerebrovasodilation associated with inhibition of nitric oxide synthase (NOS) can be reversed by exogenous NO. Rats were anesthetized (halothane) and ventilated. Neocortical cerebral blood flow (CBF) was monitored by a laser-Doppler probe. The NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg iv) reduced resting CBF [-36 +/- 5% (SE); P < 0.01, analysis of variance] and attenuated the increase in CBF elicited by hypercapnia (partial pressure of CO2 = 50-60 mmHg) by 66% (P < 0.01). L-NAME reduced forebrain NOS catalytic activity by 64 +/- 3% (n = 10; P < 0.001). After L-NAME, intracarotid infusion of the NO donor 3-morpholinosydnonimine (SIN-1; n = 6) increased resting CBF and reestablished the CBF increase elicited by hypercapnia (P > 0.05 from before L-NAME). Similarly, infusion of the guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-bromo-cGMP (n = 6) reversed the L-NAME-induced attenuation of the hypercapnic cerebrovasodilation. The NO-independent vasodilator papaverine (n = 6) increased resting CBF but did not reverse the attenuation of the CO2 response. SIN-1 did not affect the attenuation of the CO2 response induced by indomethacin (n = 6). The observation that NO donors reverse the L-NAME-induced attenuation of the CO2 response suggests that a basal level of NO is required for the vasodilation to occur. The findings are consistent with the hypothesis that NO is not the final mediator of smooth muscle relaxation in hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMed1994

Neural analogue of long-term sensitization training produces long-term (24 and 48 h) facilitation of the sensory-to-motor neuron connection in Aplysia.

1. An in vitro analogue of long-term sensitization training was used to gain insights into the mechanisms and time course of the memory for long-term sensitization in Aplysia. The analogue, consisting of four blocks of shocks, was delivered to peripheral nerves of the isolated pleural-pedal ganglia, which contain the sensory neurons and motor neurons that mediate the tail withdrawal reflex. 2. Long-term facilitation of the connections between the sensory neurons and motor neurons was produced by the conjoint stimulation of two peripheral nerves, P8 and P9. Long-term facilitation, however, was not observed after conjoint stimulation of three nerves, P7, P8, and P9. 3. The preparation was viable and stable (no changes in the amplitudes of excitatory postsynaptic potentials (EPSPs) and membrane properties in controls) for at least 48 h. Moreover, the long-term facilitation persisted for at least 48 h. 4. We observed no significant long-term changes in the resting membrane potentials of the sensory and motor neurons or in the input resistance of the motor neurons 24 and 48 h after the conjoint stimulation of nerves P8 and P9. Thus changes in these biophysical properties do not appear to contribute to the expression of long-term facilitation. 5. The finding that conjoint stimulation of three nerves, P7, P8, and P9, produced no long-term facilitation raised the possibility that stimulation of nerve P7 alone might produce long-term inhibition that opposes the facilitatory effects induced by conjoint stimulation of nerves P8 and P9. Stimulation of nerve P7 alone, however, had no long-term inhibitory effect on the EPSPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effects of pioglitazone on calcium channels in vascular smooth muscle.

Pioglitazone, an insulin-sensitizing, antidiabetic agent, has blood pressure-lowering effects in insulin-resistant hypertensive rats and attenuates growth factor-induced increases of intracellular Ca2+ in rat aortic vascular smooth muscle cells. To determine whether modulation of voltage-dependent Ca2+ channels plays a role in this association, we investigated the effects of pioglitazone on voltage-dependent current in cultured rat aortic (a7r5) and freshly dissociated rat tail artery vascular smooth muscle cells. Both cell types were studied with whole-cell patch-clamp techniques. Current through L-type Ca2+ channels was elicited with a voltage ramp in the presence of Ba2+ substituted for Ca2+. T-type Ca2+ current was studied using a two-pulse protocol that enabled the isolation of transient current. In a7r5 vascular smooth muscle cells, 2-minute application of pioglitazone (5 and 10 mumol/L) reduced L-type current by 7.9 +/- 1.0% (n = 8) (mean +/- SEM, number of cells) and 14.5 +/- 3.0% (n = 9) (P < .01, two-tailed paired t test), respectively. In contrast, 2-minute application of pioglitazone had no significant effect on T-type Ca2+ current. In freshly dissociated tail artery vascular smooth muscle cells, 2-minute application of 10 mumol/L pioglitazone had an insignificant effect (4.8 +/- 5.6% reduction); however, 25 mumol/L pioglitazone reduced L-type current by 27.3 +/- 7.2% (n = 5) (P < .01). Two-minute application of 0.1% or 0.2% dimethyl sulfoxide (vehicle) alone had no significant effects on currents in either type of vascular smooth muscle cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Rat liver macrophages express the 55 kDa tumor necrosis factor receptor: modulation by interferon-gamma, lipopolysaccharide and tumor necrosis factor-alpha.

Tumor necrosis factor-alpha is an important mediator of various inflammatory and immune responses. Its biological action is crucially dependent on interaction with specific cell surface receptors. Two different receptors for TNF-alpha with molecular masses of 55 and 75 kDa have been described. Here, the presence of a 55 kDa TNF receptor mRNA and the expression of its protein is demonstrated in rat liver Kupffer cells. TNF-alpha receptor was purified from detergent-solubilized rat Kupffer cells by adsorption to recombinant human TNF-alpha-Sepharose. One band of approx. 55 kDa was seen in SDS PAGE. An antibody raised against the 55 kDa TNF receptor bound specifically to the purified receptor as revealed by immunoblot analysis. Using Northern blotting, neither LPS nor TNF-alpha altered the expression of 55 kDa TNF-R mRNA, although the exposure of Kupffer cells to LPS decreased the binding of 125I-labelled TNF-alpha. Interferon-gamma clearly enhanced the level of 55 kDa TNF-R mRNA; this effect was abolished by transcriptional but not by translational inhibitors. The increase in 55 kDa TNF-R mRNA was maximal at 2-4 h of exposure of IFN-gamma. This cytokine also increased the binding of 125I-TNF-alpha to Kupffer cells. On the other hand, the amount of 55 kDa TNF-R transcripts was reduced after treatment with dexamethasone. These data suggest that in Kupffer cells the expression of the 55 kDa TNF-R is regulated at the transcriptional level.

Animals↗

PubMed1994

Autoperfused heart-lung preparation: one reason for unsuccessful lung preservation.

Normothermic autoperfused heart-lung preparation has the advantages of avoiding ischemic time and allowing continuous monitoring of organ function during preservation. When this technique is used, the lungs deteriorate quickly, but the reasons for this deterioration have not been investigated. This study was designed to explore the possible cause of rapid lung deterioration. Three groups of mongrel dogs were used. In Group 1 (N = 5), a buffer bag was used in the heart-lung preparation. In Group 2 (N = 6), a 20 mu filter was incorporated between the buffer bag and the right atrium. In Group 3 (N = 5), no buffer bag was used. Average survival time was 15.0 +/- 3.1 hours in Group 1, 13.5 +/- 0.7 hours in Group 2, and 21.6 +/- 2.3 hours in Group 3. Heart function was comparable among the three groups, but the arterial pulse pressure was lower and the heart rate higher in Group 3. Both white blood cell and platelet counts decreased contonuously during the preservation period. Examination of the filters in Group 2 revealed numerous aggregates consisting of platelets, white blood cells, red blood cells, and fibrin. Small thrombi were also found in the lungs in Groups 1 and 2. The results indicated that one important reason for quick lung deterioration was numerous aggregates, which were formed in the buffer bag, returned from the venous line, and trapped in the lungs. Removal of the buffer bag reduced the production of aggregates but tended to de-stabilize the hemodynamics of the preparation.

Animals↗

PubMed1994

Two-day preservation of the lungs by normothermic perfusion.

Lung function was studies during a 2-day preservation period. The lungs were removed along with the heart, liver, pancreas, duodenum, and both kidneys while they were still perfused by the heart and oxygenated by the lungs. In 12 experiments the organs survived an average of 49.2 hours. Arterial blood pressures were maintained at 74-95 mmHg, and no inotropic drugs were used. When a gas mixture of 50% O2 + 3% CO2 + 47% N2 was used, arterial oxygen tension ranged from 239 +/- 23 to 305 +/- 16 mmHg; carbon dioxide tension ranged from 17.6 +/- 1.8 to 24.9 +/- 2.9 mmHg; and pH ranged from 7.31 +/- 0.03 to 7.49 +/- 0.04. Maximum airway pressure ranged from 12.5 +/- 1.7 to 28.0 +/- 2.2 mmHg. Airway resistance ranged from 0.020 +/- 0.006 to 0.049 +/- 0.007 mmHg/ml and increased after 40 hours. Lung tissue wet/dry weight ratio was stable during the preservation period. The results showed that the lungs were well preserved in the normothermic perfusion preparation for up to two days with minimal functional changes.

Airway Resistance↗

PubMed1994

Effect of glutathione on hypothermic lung preservation.

Three groups of rats were used to test the effect of glutathione in hypothermic lung preservation. In the Normal Group (N = 8), lung function was studied immediately after removal without preservation. In the Euro-Collins (EC) Group (N = 8), the lungs were flushed with cooled Euro-Collins solution and preserved in EC solution for 24 hours. In the glutathione (GSH) Group (N = 8), glutathione (3 mM/L) was added to cooled Euro-Collins solution for perfusion and preservation. Lung function studies were performed by using living donor rats for perfusion. Venous blood from the host rat perfused the isolated lung, and the blood returned from the lung was pumped back into the internal carotid artery of the host rat. Oxygen tension in the returned blood (PvO2) in the Normal Group was higher than that in either the EC Group or the GSH Group. Pulmonary vascular resistance and airway resistance were much lower in the Normal Group than in the EC Group and GSH Group. Lung tissue wet/dry weight ratio after perfusion was 6.25 in the Normal Group, which was lower than that in the GSH Group (8.69, p < 0.05) and much lower than that in the EC Group (6.82, p < 0.05). Severe pulmonary edema and hemorrhage occurred after 30 minutes of perfusion in the EC Group, whereas a 60-minute perfusion was performed in the Normal and GSH Groups. The results indicated that rat lungs were better preserved with glutathione, but the effect was not dramatic.

Airway Resistance↗

PubMed1994

[Time-resolved fluoroimmunoassay of microalbuminuria].

Time-resolved fluoroimmunoassay (TrFIA) has been recognized as the most promising one among the so-called nonisotopic immunoassays. It is well known for its inherent advantages, high sensitivity, specificity and stability, rapid determination and wide measurement range. We have developed a new TrFIA for determining microalbumin in urine by using monoclonal anti-HSA (human serum albumin) antibody and europium label. The quality of the assay and its preliminary clinical application have been evaluated.

Adult↗

PubMed1994

[Effects of electroacupuncture on central and peripheral monoamine neurotransmitter in the course of protecting rat stress peptic ulcer].

The experimental Wistar rats were divided into two groups, the acupuncture group and the control group. Stress-induced gastric ulcer models were established by immersion of restrained rats in water. The results are as follows: 1. Stress-induced peptic ulceration was able to be protected with electroacupuncture. 2. Synthesis and decomposition of central and peripheral 5-HT in the electroacupunctured tats was inhibited. 3. The NE levels in the three brain regions (cortex, hypothalamus, brainstem) and blood were seen in the electroacupuncture group more than that in the control group, but the NE levels was smaller in the gastric tissue. 4. The higher levels of DA in the gastric tissue and blood were seen in the electroacupuncture group than in the control group. The results indicated that protecting rat stress ulceration with electroacupuncture was connected with monoamine neurotransmitter of centre and periphery.

Animals↗

PubMed1994

Effect of levcromakalim on hypoxia-, KCl- and prostaglandin F2 alpha-induced contractions in isolated rat pulmonary artery.

The effect of levcromakalim on vascular reactivity was examined in rat isolated pulmonary arterial (PA) rings. Vasoconstriction in response to KCl, prostaglandin F2 alpha (PGF2 alpha) and hypoxia and vasodilatation in response to levcromakalim were studied isometrically in a small-vessel myograph. Levcromakalim caused a dose-dependent inhibition of hypoxic pulmonary vasoconstriction (HPV) in pulmonary resistance vessels (PRV). At 10 microM, levcromakalim caused 58% inhibition in PRV compared with control. In contrast, HPV in large PAs was not significantly inhibited by levcromakalim. At a higher concentration, levcromakalim (100 microM) caused 88% inhibition in PRV and 80% inhibition in PA. The first phase of HPV is not endothelium-dependent, but second-phase contraction is partially endothelium dependent. Levcromakalim (1-10 microM) inhibited contractions induced by low KCl concentrations (10-30 mM) and had no effect on those elicited by 50 to 100 mM KCl in PRV. However, a higher concentration of levcromakalim (100 microM) significantly decreased KCl efficacy in PRV. In PA, all of the concentrations of levcromakalim (1-100 microM) significantly decreased KCl efficacy. The vasorelaxant effects of levcromakalim (1-100 microM) on PRV and PA rings contracted with a low KCl concentration (30 mM) were prevented by tetrabutylammonium (10 microns). PGF2 alpha (1-100 microM)-induced contractions were diminished in both vessel types by levcromakalim (0.1-10 microM). The maximal response to PGF2 alpha was decreased by 77.72% in PRV and 68.50% in PA, respectively, in the presence of 10 microM levcromakalim. Levcromakalim (1 microM) has no additional effect on the transient contraction induced by PGF2 alpha in Ca(++)-free solution in PRV and PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Antimalarial quinones: redox potential dependence of methemoglobin formation and heme release in erythrocytes.

A number of quinones have been shown to be effective antimalarials. In addition some have been shown to have oxidant effects on glucose-6-phosphate dehydrogenase-deficient red cells. To clarify the mechanism of this oxidant effect and to determine whether it is a general property of antimalarial quinones, the effects of five compounds on red cells were studied. Two, 5-hydroxy-6-demethyl pentaquine (5H6DP) and menadione, caused marked methemoglobin production and the insertion of heme into the red-cell membrane. The other three, atovaquone, daphnetin, and menoctone, did not. The insertion of heme into membranes caused diminished deformability, and this might account for the hemolytic effects. Redox potentials of all five compounds were measured. The two quinones that caused heme release, menadione and 5H6DP, had redox potentials of -141 +/- 12 and -97 +/- 25 mV, respectively, which are similar to the reported redox potentials for hemoglobin. The other three quinones had redox potentials that were either significantly higher or lower. Thus only quinones of the appropriate redox potentials are likely to be toxic to red cells.

Antimalarials↗

PubMed1993

Crystallization and preliminary X-ray studies of extracellular signal-regulated kinase-2/MAP kinase with an incorporated His-tag.

The extracellular signal-regulated kinase ERK2, a member of the protein kinase superfamily, phosphorylates a variety of cellular proteins in response to extracellular signals. ERK2 expressed in Escherichia coli as a fusion protein with the sequence Ala-His6 at the N terminus has low basal activity and very low levels of phosphate incorporation, but can be fully activated. The Ala-His6 ERK2 as expressed in the unphosphorylated form has been crystallized in space group P2(1). The cell constants are a = 49.32 A, b = 71.42 A, c = 61.25 A, and beta = 109.75 degrees, and the crystals diffract to better than 1.8 A resolution.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1993

Complementation of transport-deficient mutants of Escherichia coli alpha-hemolysin by second-site mutations in the transporter hemolysin B.

Hemolysin B (HlyB) is a membrane-bound transport protein composed of an amino-terminal multiple membrane-spanning portion followed by a conserved ATP binding sequence. Together with the inner membrane protein HlyD and the outer membrane protein TolC, HlyB is responsible for transport of the 107-kDa toxin HlyA from the cytoplasm, across both membranes of the cell envelope of Escherichia coli, directly to the medium. We have used a mutational approach to investigate a postulated interaction between HlyA and HlyB. We have isolated transport-deficient mutants of HlyA altered in the C-terminal signal sequence and used one of these, a deletion of 29 amino acids, to select compensatory mutants in the transporter protein HlyB. Fifteen mutants located at six different sites, all mapping within the amino-terminal multiple membrane-spanning domain of HlyB, were identified. All of the mutations are clustered into three groups located close to the predicted inner face of the cytoplasmic membrane. We propose that these locations are close to sites on HlyB that interact with the C-terminal signal sequence of HlyA. This interaction is likely to involve either binding of HlyA to HlyB or activation of the transport mechanism. The compensatory mutants also display different patterns of specificity in terms of their ability to transport different HlyA mutants. The fact that point mutations are able to compensate for drastic changes in the signal sequence of HlyA suggests that substrate specificity of transporters such as HlyB may shift dramatically during evolutionary history. This could account for the diversity of substrates observed for the ABC transporter superfamily in nature.

Amino Acid Sequence↗

PubMed1993

Functional replacement of the hemolysin A transport signal by a different primary sequence.

Secretion of the 107-kDa hemolysin A (HlyA) from Escherichia coli is mediated by the membrane proteins hemolysin B and hemolysin D. Hemolysin B is a member of the so-called ATP binding cassette transporter superfamily, which includes the multidrug resistance P-glycoprotein, the cystic fibrosis CFTR protein, and the major histocompatibility complex-associated transporter of antigenic peptides. Recognition of HlyA by the hemolysin B/D transporter is dependent on a signal sequence mapped to the C-terminal 50 or so amino acids of the HlyA molecule. We show that the C-terminal 70 amino acids of leukotoxin from Pasteurella hemolytica can substitute functionally for the HlyA signal sequence. This 70-amino acid sequence contains no primary sequence similarity to the HlyA signal sequence; however, structural motifs of helix-turn-helix followed by strand-loop-strand can be deduced for both sequences. We also demonstrate by site-directed mutagenesis that changes to these predicted motifs affect transport function. It thus appears that the transport signal of HlyA may be defined by a higher-order structure and that the hemolysin transporter may recognize a much wider diversity of primary sequences than previously anticipated. This finding may have implications for understanding the basis of substrate specificity of other ATP binding cassette transporters.

Adenosine Triphosphate↗

PubMed1993

Thermodynamics of binding of the CO2-competitive inhibitor imidazole and related compounds to human carbonic anhydrase I: an isothermal titration calorimetry approach to studying weak binding by displacement with strong inhibitors.

The visible spectrum of Co(II)-substituted human carbonic anhydrase I (HCA I) complexed with the unique CO2-competitive inhibitor imidazole undergoes a marked alkaline intensification, with a midpoint near pH 8 [Bauer, R., Limkilde, P., & Johansen, J. T. (1977) Carlsberg Res. Commun. 42, 325-339]. This change was first attributed to the ionization of a nondisplaced water ligand of the active-site metal in a five-coordinate complex. Later proposals favored assigning it to the deprotonation of the bound imidazole itself to give a tetrahedrally coordinated imidazolate anion at high pH. We have determined by isothermal titration calorimetry the pH dependence of the enthalpy of binding of imidazole and its analogues to HCA I and Co(II)HCA I. We devised an indirect strategy whereby the enthalpy of binding of the strong sulfonamide inhibitor methazolamide was determined in the absence and presence of a constant high concentration of the competing imidazole or its analogues. The standard enthalpy of binding of deprotonated methazolamide to the "acid" form of HCA I and Co(II)HCA I was found to be pH independent over the pH range of 6.5-9.5, as expected. It was also identical for both the zinc (-13.5 +/- 1.1 kcal M-1) and the cobalt (-13.7 +/- 0.4 kcal M-1) forms. The standard enthalpy of binding of neutral imidazole (average value -6.1 +/- 0.8 kcal M-1) surprisingly did not show any marked pH dependence, varying by about 1.1 and 2.6 kcal M-1 for the zinc and cobalt enzymes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding, Competitive↗

PubMed1993

Nitric oxide synthase-containing neural processes on large cerebral arteries and cerebral microvessels.

We studied whether neural processes containing nitric oxide synthase (NOS) are associated with large cerebral arteries and/or intraparenchymal microvessels. The presence of NOS-positive nerves on large cerebral arteries was examined in whole-mount preparations processed for NADPH diaphorase histochemistry, a procedure that stains NOS-containing neurons. The association between NOS-containing neural processes and intracerebral microvessels was studied by electron microscopy in ultrathin brain sections reacted with antibodies against NOS. A dense perivascular plexus of NADPH diaphorase positive axons was observed in the anterior portion of the circle of Willis and its branches while in the basilar artery the innervation was less dense. Lesions of the major sources of perivascular innervation of the cerebral arteries indicated that these nerve fibers arise from the sphenopalatine ganglia. Within the brain parenchyma, NOS immunoreactivity was observed in dendrites and axonal terminals closely associated with the basal lamina of arterioles and capillaries. We conclude that NOS-containing nerves of peripheral origin innervate large cerebral arteries while NOS-containing neural processes of central origin, especially dendrites, are closely associated with cerebral arterioles and capillaries. The presence of NOS in perivascular dendrites raises the possibility that these structures are a major source of NO during neural activity. These findings, collectively, provide morphological evidence supporting the hypothesis that NOS neurons participate in the mechanisms that match neural activity to cerebral blood flow.

Amino Acid Oxidoreductases↗