Inhibitory Effects of Anesthetics on Cyclic Guanosine Monophosphate (cGMP) Accumulation in Rat Cerebellar Slices

Terasako, Kiyoshi; Nakamura, Kumi; Miyawaki, Ikuko; Toda, Hiroshi; Kakuyama, Masahiro; Mori, Kenjiro

doi:10.1213/00000539-199411000-00018

Cited by 53 publications

(17 citation statements)

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“…In our study using isolated rat aorta [4], these anesthetics suppressed cGMP formation induced by nitric oxide (NO) or by an NO-donor drug (sodium nitroprusside, SNP), being consistent with the findings of Jing et al [5]. In another study of ours using rat cerebellar slices [6], halothane, at concentrations that suppressed the formation of cGMP induced by N-methyl daspartate (NMDA) and d-aspartate, did not alter the effects induced by SNP. Masaki and Kondo suspected that the concentration of SNP we used (0.3 mM) was a supramaximal one [1], but under our experimental conditions, SNP continued to increase cGMP levels in a concentration-dependent manner at least up to 10 mM [7].…”

supporting

confidence: 90%

“…Moreover, both d-aspartate (1 mM) and SNP (0.3 mM) increased cGMP to similar levels, and halothane suppressed only the increase induced by daspartate [6]. I do not believe, however, that the results of Masaki and Kondo [1] or Jing et al [5] conflict with ours [4,6]. Rather, when the findings of the above four papers are considered together, it is apparent that halothane suppresses GC activity, but that some site or mechanism between the glutamate receptor and NO formation is more susceptible to halothane than GC activity itself.…”

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confidence: 86%

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Implications of the suppression of guanylate cyclase activity by halothane

Nakamura

1999

Journal of Anesthesia

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To the editor: I read with interest the paper by Masaki and Kondo [1] and the subsequent discussion with Terasako [2,3]. Masaki and Kondo demonstrated clearly that halothane and sevoflurane (at concentrations greater than 0.222 and 0.812 mM, respectively) suppress the activity of soluble guanylate cyclase (GC) isolated from rat brain. In our study using isolated rat aorta [4], these anesthetics suppressed cGMP formation induced by nitric oxide (NO) or by an NO-donor drug (sodium nitroprusside, SNP), being consistent with the findings of Jing et al. [5]. In another study of ours using rat cerebellar slices [6], halothane, at concentrations that suppressed the formation of cGMP induced by N-methyl daspartate (NMDA) and d-aspartate, did not alter the effects induced by SNP. Masaki and Kondo suspected that the concentration of SNP we used (0.3 mM) was a supramaximal one [1], but under our experimental conditions, SNP continued to increase cGMP levels in a concentration-dependent manner at least up to 10 mM [7]. Moreover, both d-aspartate (1 mM) and SNP (0.3 mM) increased cGMP to similar levels, and halothane suppressed only the increase induced by daspartate [6]. I do not believe, however, that the results of Masaki and Kondo [1] or Jing et al. [5] conflict with ours [4,6]. Rather, when the findings of the above four papers are considered together, it is apparent that halothane suppresses GC activity, but that some site or mechanism between the glutamate receptor and NO formation is more susceptible to halothane than GC activity itself. The locus of action is possibly one of the mechanisms coupled to the glutamate receptor.

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confidence: 90%

mentioning

confidence: 86%

Implications of the suppression of guanylate cyclase activity by halothane

Nakamura

1999

Journal of Anesthesia

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“…51,52 However, in the studies that used rat brain homogenates, isoflurane was added to the incubation mixture rather than given in vivo to the intact animal. 52 In the present study (Figure 2, top panel) we did not find evidence of inhibition of NOS using a sham protocol when isoflurane was given for 1.5 or 2.0 hours.…”

Section: Core and Penumbral Nos Activity In Isoflurane Sham Groupsmentioning

confidence: 99%

Core and Penumbral Nitric Oxide Synthase Activity During Cerebral Ischemia and Reperfusion

Ashwal

Tone

Tian

et al. 1998

Stroke

251

123

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Background and Purpose-The present studies examined the hypothesis that the distribution of cerebral injury after a focal ischemic insult is associated with the regional distribution of nitric oxide synthase (NOS) activity. Methods-Based on previous studies that certain anatomically well-defined areas are prone to become either core or penumbra after middle cerebral artery occlusion (MCAO), we measured NOS activity in these areas from the right and left hemispheres in a spontaneously hypertensive rat filament model. Four groups were studied: (1) controls (immediate decapitation); (2) 1.5 hours of MCAO with no reperfusion (R0); (3) 1.5 hours of MCAO with 0.5 hour of reperfusion (R0.5); and (4) 1.5 hours of MCAO with 24 hours of reperfusion (R24). Three groups of corresponding isoflurane sham controls were also included: 1.5 (S1.5) or 2 (S2.0) hours of anesthesia and 1.5 hours of anesthesiaϩ24 hours of observation (S24). Results-Control core NOS activity for combined right and left hemispheres was 129% greater than penumbral NOS activity (PϽ0.05). Combined core NOS activity was also greater (PϽ0.05) in the three sham groups: 208%, 122%, and 161%, respectively. In the three MCAO groups, ischemic and nonischemic core NOS remained higher than penumbral regions (PϽ0.05). However, NOS activity was lower in the ischemic than in the nonischemic core in all three groups: R0 (29% lower), R0.5 (48%), and R24 (86%) (PϽ0.05). Addition of cofactors (10 mol/L tetrahydrobiopterin, 3 mol/L flavin adenine dinucleotide, and 3 mol/L flavin mononucleotide) increased NOS activity in all groups and lessened the decrease in ischemic core and penumbral NOS. Conclusions-Greater NOS activity in core regions could explain in part the increased vulnerability of that region to ischemia and could theoretically contribute to the progression of the infarct over time. The data also suggest that NOS activity during ischemia and reperfusion could be influenced by the availability of cofactors.

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“…15,16 However, the role of NO in normal baroreflex regulation in the RVLM remains elusive, because this messenger has been found to have little effect on baroreflexes in control anesthetized animals. 11,16 Given that anesthesia and surgical stress may be limiting factors in studying the effects of NO signaling, 17,18 the current study aimed to determine the effect of NO on sympathetic and cardiac baroreflexes in the RVLM of conscious, chronically instrumented rabbits. The role of local nNOS and iNOS in the tonic and reflex control of blood pressure was also examined in this study.…”

mentioning

confidence: 99%

Selective Sensitization by Nitric Oxide of Sympathetic Baroreflex in Rostral Ventrolateral Medulla of Conscious Rabbits

Mayorov

2005

Hypertension

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Abstract-Nitric oxide (NO) deficiency in the rostral ventrolateral medulla (RVLM) has been implicated in impaired baroreflex control in hypertensive and heart failure animals. However, the role of local NO in normal baroreflex regulation remains unclear. This study aimed to examine the role of NO in tonic and baroreflex control of blood pressure (BP) in the RVLM of conscious rabbits. Microinjections of NO donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside (5 to 20 nmol), or NO itself (20 to 200 pmol) into the RVLM dose-dependently increased BP. Bilateral microinjections of an NO synthase (NOS) inhibitor N G -nitro-L-arginine methyl ester (L-NAME; 10 nmol), its inactive enantiomer D-NAME, or soluble guanylate cyclase (sGC) inhibitors, 1-H-[1,2,4]oxadiaolo[4,3-a]quinoxalin-1-one (ODQ, 250 pmol) and methylene blue (10 nmol), into the RVLM did not affect resting BP, heart rate, or renal sympathetic nerve activity (RSNA). However, L-NAME, methylene blue, and ODQ decreased RSNA baroreflex gain by 42% to 55%, whereas D-NAME did not affect this reflex. Co-microinjections of L-NAME and superoxide scavenger tempol (20 nmol) decreased RSNA baroreflex gain by 37Ϯ8%. Microinjections of a neuronal NOS (nNOS) inhibitor, 7-nitroindazole (500 pmol), into the RVLM decreased RSNA baroreflex gain by 42Ϯ12%, without altering resting BP, heart rate, or RSNA. Local administration of inducible NOS (iNOS) inhibitors, S-methylisothiourea (0.25 nmol) and aminoguanidine (0.25 and 2.5 nmol), affected neither resting nor baroreflex parameters. These results suggest that nNOS-derived NO facilitates sympathetic baroreflex transmission in the RVLM at least in part via a sGC-dependent, superoxide-independent mechanism. However, local nNOS and iNOS play little role in the tonic support of BP in conscious rabbits. One brain region where NO may be of primary importance in cardiovascular control is the rostral ventrolateral medulla (RVLM), which is thought to be a final common pathway for regulating sympathetic activity. 4 Microinjections of NO donors into this region, unless given in high doses, 5 increase blood pressure in a sGC-dependent manner in conscious 6,7 and anesthetized animals. 5,8,9 By contrast, local administration of NOS and sGC inhibitors decrease or block the hypertensive responses to EAAs 5,6,10 and also attenuate various cardiovascular reflexes. 11,12 Importantly, NO may also play a role in the tonic support of blood pressure in the RVLM. 9,13 In particular, it has been shown that NO derived from the neuronal (nNOS) and inducible (iNOS) isoforms of NOS exerts, respectively, excitatory and inhibitory actions in the RVLM, 9 and the balance between these actions is shifted toward excitation in hypertensive animals. 14 Recent evidence suggests that NO deficiency in the RVLM may underlie impaired baroreflex regulation in such disease states as hypertension and heart failure. 15,16 However, the role of NO in normal baroreflex regulation in the RVLM remains elusive, because this messenger has been found to have little effec...

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Inhibitory Effects of Anesthetics on Cyclic Guanosine Monophosphate (cGMP) Accumulation in Rat Cerebellar Slices

Cited by 53 publications

References 0 publications

Implications of the suppression of guanylate cyclase activity by halothane

Implications of the suppression of guanylate cyclase activity by halothane

Core and Penumbral Nitric Oxide Synthase Activity During Cerebral Ischemia and Reperfusion

Selective Sensitization by Nitric Oxide of Sympathetic Baroreflex in Rostral Ventrolateral Medulla of Conscious Rabbits

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