• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.2
• /
• pp.73-77
• /
• 2003

The effects of nitric oxide on the vestibular function recovery following unilateral labyrinthectomy (UL) were studied. Sprague-Dawley male rats, treated with nitric oxide liberating agent sodium nitroprusside (SNP) and NOS inhibitor $N^G$-nitro-L-arginine methyl ester (L-NAME), were subjected to destruction of the unilateral vestibular apparatus, and then spontaneous nystagmus was observed in the rat. To explore the effects of nitric oxide on the neuronal excitability, whole cell patch clamp technique was applied on isolated medial vestibular nuclear neurons. The frequency of spontaneous nystagmus in SNP treated rats was lesser than that of spontaneous nystagmus in control animals. In contrast, pre-UL treatment with L-NAME resulted in a significant increase in spontaneous nystagmus frequency. In addition, SNP increased the frequency of spontaneous action potential in isolated medial vestibular nuclear neurons. Potassium currents of the vestibular nuclear neurons were inhibited by SNP. After blockade of calcium dependent potassium currents by high EGTA (11 mM) in a pipette solution, SNP did not inhibit outward potassium currents. 1H-[1,2,4] oxadiazolo [4,3-a] quinozalin-1-one (ODQ), a specific inhibitor of soluble guanylyl cyclase, inhibited the effects of SNP on the spontaneous firing and the potassium current. These results suggest that nitric oxide after unilateral labyrinthectomy would help to facilitate vestibular compensation by inhibiting calcium-dependent potassium currents through increasing intracellular cGMP, and consequently would increase excitability in ipsilateral vestibular nuclear neurons.

• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.2
• /
• pp.85-89
• /
• 2003

The basic mechanism for the excitation of the peripheral vestibular receptors following acute hypotension induced by sodium nitroprusside (SNP) or hemorrhage was investigated in anesthetized rats. Electrical activity of the afferent vestibular nerve was measured after pretreatment with kynurenic acid, an NMDA receptor antagonist. The activity of the vestibular nerve at rest following acute hypotension induced by SNP or simulating hemorrhage was a greater increase than in control animals. The gain of the vestibular nerve with sinusoidal rotation following acute hypotension increased significantly compared to control animals. The acute hypotension induced by SNP or hemorrhage did not change the activity of the afferent vestibular nerve after kynurenic acid injection. These results suggest that acute hypotension produced excitation of the vestibular hair cells via glutamate excitotoxicity in response to ischemia.

• Korean Journal of Veterinary Research
• /
• v.57 no.3
• /
• pp.181-187
• /
• 2017

Antihypertensive effects of ethanol extracts of Aralia elata (Miq.) Seem. (AE) were investigated in spontaneously hypertensive rats (SHR). SHR aged 14 weeks were treated for 8 weeks with AE (10 or 50 mg/kg/day) or amlodipine besylate (Am; 10 mg/kg/day) orally. Hypertension results in injury to several organs and can produce a significant increase in malondialdehyde (MDA) content as a result of lipid peroxidation and endothelial dysfunction. In this study, oral administration of AE and Am significantly reduced systolic blood pressure, organ weight index, and MDA content in tissues but increased significantly the plasma nitrite and nitrate concentrations. The endothelium-dependent relaxant activities of acetylcholine ($10^{-10}-10^{-3}M$) in norepinephrine (NE)-precontracted aorta were increased in AE- and Am-treated rats. Particularly strong endothelium-dependent relaxant activities were observed in AE-treated (50 mg/kg) rats. The endothelium-independent relaxant activities of sodium nitroprusside ($10^{-10}-10^{-3}M$) in NE-precontracted aorta were not changed. The results of this study suggest that AE has both antihypertensive and end-organ protective effects in SHR.

• Journal of Microbiology
• /
• v.35 no.2
• /
• pp.152-157
• /
• 1997

Infection of human fibroblast (HF) cells with human cytomegalovirus (HCMV) result in changes in the intracellular level of second messengers. Since nitric oxide (NO) production has been known to be related with other second messengers, it is probable that HCMV infection of HF cells may involve NO. To test this possibility, the amount of NO was measured following ogenous addition of NO generators such as sodium nitroprusside (SNP) or S-nitroso-N-a-cetylpenicillamine (SNAP) immediately after HCMV infection, however, inhibited virus multiplication. Furthermore, immunoblot experiment using monoclonal antibody to HCMV major immediate early (MIE) proteins or CAT assay using pCMVIE/CAT (plasmid containing CAT gene driven by HCMV MIE promoter) revealed that SNP or SNAP blocked the MIE gene expression. SNP was more effective than SNAP in hibiting HCMV multiplication or MIE gene expression. SNP produced more NO than SNAP in inhibiting HCMV multiplication or MIE gene expression. SNP produced more NO than SNAP. Although the mechanism for the inhibition of HCMV multiplication and MIE gene expression by NO is still elusive some correlation with NO-mediated inhibition of HCMV-induced increase in cytosolic free Ca$\^$2+/ concentration ([Ca$\^$2+/]) was observed. The increase of [Ca$\^$2+/] following HCMV infection was inhibited by SNP, and less effectively by SNAP. Raising [Ca$\^$2+/ with bromo-A23187 partially reversed the SNP block of MIE gene expression. Thus, there appear to e some relationships among NO. [Ca$\^$2+/], and HCMV MIE gene expression.

• Biomolecules & Therapeutics
• /
• v.3 no.2
• /
• pp.149-153
• /
• 1995

Nitric oxide (NO) has been regarded as one of the neurotransmitters of nonadrenergic, noncholinergic (NANC) nerve stimulation in rabbit corpus cavernosum, rat gastric fundus and human intestine. PIANO (photo-induced adequate nitric oxide) is a very useful tool to investige the role of NO in various smooth muscles where NO is a mediator. The present study was undertaken to compare the physiological responses of the rat gastric smooth muscle in response to NANC nerve stimulation and to PIANO. Photolysis of L-NAME, D-NAME and streptozotocin (572) by UV light in the bathing medium caused relaxation of rat gastric fungus that contracted with carbachol, but was resistant to tetrodotoxin (TTX, 1 $\mu$M). Electrical stimulation (20 V, 2~32 Hz, 0.2 msec, 10s) of the gastric fundus, in the presence of atropine and guanethidine, induced frequency-dependent, TTX-sensitive relaxation. Sodium nitroprusside (1 nM-10 $\mu$M), a NO donor, mimicked the relaxations observed after NANC-stimulation or PIANO. Furthermore, PIANO caused UV light exposure time-dependent increase of CGMP in rat gastric fungus strips. These results provide another evidence indirectly that NO is one of the mediators of the NANC inhibitory nerve stimulation in the rat gastric fundus.

• Advances in Traditional Medicine
• /
• v.3 no.4
• /
• pp.205-211
• /
• 2003

Stem bark of Cinchona sp. (Rubiaceae) is one of the well known drugs for its therapeutic values in traditional as well as modern medicine. Even though a lot of work has been carried out on quinoline alkaloids of Cinchona, its phenolic constituents received very little attention. In the present study, we evaluated antioxidant properties of C. officinalis stem bark methanolic extract and water extract containing phenolic compounds (total phenolics 21.37, 5.18% w/w respectively in the two extracts) in different in vitro and ex vivo models viz., antiradical activity by DPPH reduction, superoxide radical scavenging activity in riboflavin/light/NBT system, nitric oxide radical scavenging activity in sodium nitroprusside/Greiss reagent system and inhibition of lipid peroxidation induced by iron-ADP-ascorbate in liver homogenate and haemolysis of erythrocytes induced by phenylhydrazine in erythrocyte membrane stabilization study. Both the extracts exhibited very good antioxidant activity in all the models tested. The phenolic compounds including tannins present in the stem bark seem to offer protection from the oxidative damage.

• Archives of Pharmacal Research
• /
• v.21 no.3
• /
• pp.315-319
• /
• 1998

Gastric smooth muscle of cats was used to investigate the involvement of protein kinase in vanadate-induced contraction. Vanadate caused a contraction of cat gastric smooth muscle in a dose-dependent manner. Vanadate-induced contraction was totally inhibited by 2 mM EGTA and 1.5 mM $LACI_3$ and significantly inhibited by $10\mu$M verapamil and $1\mu$M nifedipine, suggesting that vanadate-induced contraction is dependent on the extracellular $Ca^{2+}$ concentration, and the influx of extracellular $Ca^{2+}$ was mediated through voltage-dependent $Ca^{2+}$ channel. Both protein kinase C inhibitor and tyrosine kinase inhibitor significantly inhibited the vanadate-induced contraction and the combined inhibitory effect of two protein kinase inhibitors was greater than that of each one. But calmodulin antagonists did not have any influence on the vanadate-induced contraction. On the other hand, both forskolin ($1\mu$M) and sodium nitroprusside ($1\mu$M) significantly inhibited vanadate-induced contraction. Therefore, these results suggest that both protein kinase C and tyrosino kinase are involved in the vanadate-induced contraction which required the influx of extracellular $Ca^{2+}$ in cat gastric smooth muscle, and that the contractile mechanism of vanadate may be different from that of agonist binding to its specific receptor.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1992.05a
• /
• pp.33-33
• /
• 1992

항혈전성 약물로서 그의 항 혈소판 작용력은 dipyridamole보다 강하나 심혈관계 등에 대한 부작용이 적어 clinical efficiency가 유의하게 높은 약물개발에 대한 연구는 임상적 응용성 뿐 아니라, 혈소판-응고기전의 규명에 기여할 것으로 사료되는 바 본 연구에서는 cyclic nucleotide phosphodiesterase(PDE-I)들의 항혈소판 작용을 검토하여 그들의 혈관 내피세포와 혈관평활 근세포의 중식에 대한 영향을 항혈소판성 작용을 보이며 혈관세포들의 증식에 없어서는 안되는 spermine의 그것과 비교 검색하였다. Johnson 등(1985)의 방법에 따라서 제조한 aequorin부하-가토혈소판의 thrombin(0.25 units: TB)에 대한 응집반응에서, pyridazinone 유도체인 KR30075, sodium nitroprusside(SNP), imazodan, isobutylmethylxanthine(IBMX), rolipram, 및 spermine의 응집억제성 $IC_{50}$/ (M)은 각각 2.21 $\times$ $10^{-7}$, 1.26 $\times$ $10^{-6}$, 6.96 $\times$ $10^{-6}$, 7.78 $\times$ $10^{-6}$, 8.11 $\times$ $10^{-4}$, 및 4.28 $\times$ $10^{-3}$ M으로써 이들은 TB-응고반응에 동반되는 혈소판 [Ca$^{++}$]$_{i}$-증가에 대한 각각의 $IC_{50}$/과 차이를 보이지 않았으며, 유의한 상관성을 보였다.

• International Journal of Oral Biology
• /
• v.40 no.4
• /
• pp.211-216
• /
• 2015

Nitric Oxide (NO) is an important signaling molecule in the nociceptive process. Our previous study suggested that high concentrations of sodium nitroprusside (SNP), a NO donor, induce a membrane hyperpolarization and outward current through large conductances calcium-activated potassium ($BK_{ca}$) channels in substantia gelatinosa (SG) neurons. In this study, patch clamp recording in spinal slices was used to investigate the sources of $Ca^{2+}$ that induces $Ca^{2+}$-activated potassium currents. Application of SNP induced a membrane hyperpolarization, which was significantly inhibited by hemoglobin and 2-(4-carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (c-PTIO), NO scavengers. SNP-induced hyperpolarization was decreased in the presence of charybdotoxin, a selective $BK_{Ca}$ channel blocker. In addition, SNP-induced response was significantly blocked by pretreatment of thapsigargin which can remove $Ca^{2+}$ in endoplasmic reticulum, and decreased by pretreatment of dentrolene, a ryanodine receptors (RyR) blocker. These data suggested that NO induces a membrane hyperpolarization through $BK_{ca}$ channels, which are activated by intracellular $Ca^{2+}$ increase via activation of RyR of $Ca^{2+}$ stores.

• Food Science and Biotechnology
• /
• v.18 no.1
• /
• pp.167-171
• /
• 2009

This study examined the antioxidative activity of delphinidin, a kind of anthocyanidin from eggplant. Cellular protective potential from oxidative damage by nitric oxide (NO), superoxide anion ($O_2^-$), and peroxynitrite ($ONOO^-$) using epithelial cell line LLC-PK1 cell as well as in vitro radical scavenging effects were investigated. Delphinidin showed strong in vitro radical scavenging effects against NO, $O_2^-$, and hydroxyl radical (${\cdot}OH$) in dose-dependent manners. In addition, delphinidin increased cell viability in LLC-PK1 cells in a concentration-dependent manner when viability was reduced by $ONOO^-$-induced oxidative damage. To elucidate the protective mechanisms of delphinidin from $ONOO^-$, sodium nitroprusside (SNP), and pyrogallol were also employed to generate NO and $O_2^-$, respectively. The treatment of delphinidin recovered reductions in cell viability caused by SNP and pyrogallol, indicating that delphinidin can attenuate oxidative stress induced by NO and $O_2^-$. The present study suggests that delphinidin is a promising anti oxidative agent.