• The Korean Journal of Zoology
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• v.36 no.3
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• pp.433-438
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• 1993

In the previous paper (Choi et al., 1992), we found that a large but transient elevation in intracellular cGMP levels occur concomitant with the myoblast fusion. To establish the physiological significance of the elevation of cGMP levels, the change in guanylate cyclase activity dudng myoblast fusion and the correlation hetween various chemicals that may affect guanylate cyclase adivity and myoblast fusion were examined. Sodium nitroprusside, a nitric oxide-forming compound, induced a precocious fusion and increased guanylate cyclase activity compared to the control. Furthermore, L-NG-monomethyl arginine, specific inhibitor of L-arginine: nitric oxide synthase, inhibited the cell fusion in a dose-dependent manner, without affecting biochemical differentiation. On the basis of our present findings, we propose that the onset of myoblast fusion is somehow correlated with the rise in cellular cGMP levels that is regulated by the activation or inhibItIon of soluble guanylate cyclase, via as yet undefined mechanism but possibly through L-arginine: nitric oxide pathway.

• Journal of Acupuncture Research
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• v.26 no.2
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• pp.31-40
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• 2009

Objectives: The purpose of this study is to investigate the effects of Daedon($LR_1$) Supplementation and Eumgok($KI_{10}$) Draining on changes of cerebral blood flow in normal rats. Methods : Regional cerebral blood flow(rCBF) and mean arterial blood pressure(MABP) in normal rats are observed, and those mechanisms were also investigated with pre-treatment of indomethacin (IDM) and methylene blue(MTB) each. Results : In this study, $LR_1$ supplementation and $KI_{10}$ draining elevated level of rCBF after 30 min, but MABP level was lowered at 30 min, then recovered toward normal level. Pre-treatment with indomethacin (IDM), an inhibitor of cyclooxygenase, inhibited increase of rCBF effectively, and pre-treatment with methylene blue(MTB), an inhibitor of guanylate cyclase, also inhibited increase of rCBF levels. On the other hand pre-treatment with IDM or MTB did not affect MABP levels. Conclusions : In conclusion, these results suggest that $LR_1$ supplementation and $KI_{10}$ draining can increase rCBF, and the mechanisms are thought to be related to both of cyclooxygenase and Guanylate cyclase pathways.

• Journal of Pharmacopuncture
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• v.16 no.4
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• pp.30-35
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• 2013

Objectives: This study was designed to investigate the effects of Calculus Bovis-Fel Uris-Moschus pharmacopuncture (BUM) on the regional cerebral blood flow (rCBF) and the mean arterial blood pressure (MABP) in normal and cerebral ischemic rats and to investigate a possible pathway involved in the effects of BUM. Methods: The changes in the rCBF and the MABP following BUM into Fengfu (GV16) were determined by using a laser-Doppler flow meter and a pressure transducer, respectively. Results: BUM significantly increased the rCBF and decreased the MABP in normal rats in a dose-dependent manner. The effect on the rCBF was significantly inhibited by pretreatment with methylene blue (0.01 mg/kg, intraperitoneal), an inhibitor of guanylate cyclase, but was not affected by pretreatment with indomethacin (1 mg/kg, intraperitoneal), an inhibitor of cyclooxygenase. The BUM-induced decrease of the MABP was changed neither by methylene blue nor by indomethacin pretreatment. In the cerebral ischemic rats, the rCBF was stably increased upon cerebral reperfusion in the BUM group in contrast to the rapid and marked increase in the control group. Conclusion: This study demonstrated that BUM into Fengbu (GV16) increased the rCBF in a dose-dependent manner in the normal state; furthermore, it improved the stability of the rCBF in the ischemic state upon reperfusion. Also, the effects of BUM on the rCBF were attenuated by inhibition of guanylate cyclase, suggesting that the effects involved the guanylate cyclase pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.343-351
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• 2001

This study was undertaken to investigate the mechanism of lipopolysaccharide (LPS) and nitric oxide (NO) as a regulator of vascular smooth muscle cell (VSMC) proliferation. VSMC was primarily cultured from rat aorta and confirmed by the immunocytochemistry with anti-smooth muscle myosin antibody. The number of viable VSMCs were counted, and lactate dehydrogenase (LDH) activity was measured to assess the degree of cell death. Concentrations of nitrite in the culture medium were measured as an indicator of NO production. LPS was introduced into the medium to induce the inducible nitric oxide synthase (iNOS) in VSMC, and Western blot for iNOS protein and RT-PCR for iNOS mRNA were performed to confirm the presence of iNOS. Inhibitors of iNOS and soluble guanylate cyclase (sGC), sodium nitroprusside (SNP) and L-arginine were employed to observe the action of LPS on the iNOS-NO-cGMP signalling pathway. LPS and SNP decreased number of VSMCs and increased the nitrite concentration in the culture medium, but there was no significant change in LDH activity. A cell permeable cGMP derivative, 8-Bromo-cGMP, decreased the number of VSMCs with no significant change in LDH activity. L-arginine, an NO substrate, alone tended to reduce cell count without affecting nitrite concentration or LDH level. Aminoguanidine, an iNOS specific inhibitor, inhibited LPS-induced reduction of cell numbers and reduced the nitrite concentration in the culture medium. LY 83583, a guanylate cyclase inhibitor, suppressed the inhibitory actions of LPS and SNP on VSMC proliferation. LPS increased amounts of iNOS protein and iNOS mRNA in a concentration-dependent manner. These results suggest that LPS inhibits the VSMC proliferation via production of NO by inducing iNOS gene expression. The cGMP which is produced by subsequent activation of guanylate cyclase would be a major mediator in the inhibitory action of iNOS-NO signalling on VSMC proliferation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.2
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• pp.173-182
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• 2013

This Study was designed to investigate the effects of Sibjeondaebo-tang (SDT) and Gamy-Sibjeondaebo-tang (GST, Sibjeondaebo-tang adding Cervi Pantotrichum Cornu) on the improvement in regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats, and in the rats with cerebral ischemia induced by middle cerebral artery occlusion, and further to determine the mechanisms. And, It was to investigate the effects of the SDT and GST with the change of histologic examination through the BDNF in the hippocampus CA1. In changes of cerebral hemodynamics, SDT and GST significantly increased rCBF in a dose-dependent manner but decreased MABP in normal rats. In mechanism of cerebral hemodynamics, Increase of GST-induced rCBF was significantly inhibited by pretreatment with methylene blue (0.01 mg/kg, i.p.), an inhibitor of guanylate cyclase, and Decrease of GST-induced MABP was significantly increased by pretreatment with methylene. These results suggested that the action of GST was mediated by guantlate cyclase pathway. In cerebral ischemics, the rCBF was stably improved by SDT (10 mg/kg, i.p.) significantly and stably increased by GST (10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrast with the findings of rapid and marked increase in Control group. These results suggested that GST had anti-ischemic action in cerebral ischemic state. In histological examination through TTC stain, Sample A group and Sample B group decreased discoloration in the cortical part at $28^{th}$ day after MCAO induction. In immunohistochemistric response of BDNF, Sample A group and Sample B group increased respondent effect at $28^{th}$ day after MCAO induction. These results suggest that GST can Increase rCBF in normal state, as well as improve the stability of rCBF in cerebral ischemic state. Furthermore, methylene blue inhibitor study suggested the mechanism of blood flow enhancement by GST may be mediated by guanylate cyclase pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.50-56
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• 2009

The present study was designed to investigate the effects of Phamacopuncture therapy using Cervi Pantotrichum Cornu (PC) at BL23 BL52 on the regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats, then the related mechanisms were also investigated. In addition, the present author also investigated the effects of phamacopuncture therapy at BL23.BL52 on the rCBF in cerebral ischemic rats. The results in normal rats were as follows; PC (3 mg/kg and 5 mg/kg) at BL23 BL52 significantly increased rCBF but decreased MABP. This result suggests that PC at BL23 BL52 significantly increased rCBF by dilating pial arterial diameter. Increase of PC (5 mg/kg)-induced rCBF was significantly inhibited by pretreatment with indomethacin (1 mg/kg, i.p.), an inhibitor of cyclooxygenase and methylene blue ($10{\mu}g/kg$, i.p.), an inhibitor of guanylate cyclase. Decrease of PC (5 mg/kg)-induced MABP was significantly increased by pretreatment with methylene blue but was decreased by pretreatment with indomethacin. These results suggested that the action of PC (5 mg/kg) was mediated by guanylate cyclase. The results in cerebral ischemic rats were as follows ; The rCBF was significantly and stably increased by PC (5 mg/kg) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in Control group. In conclusion, these results suggest that phamacopuncture therapy using Carthami flos at BL23 BL52 can increase rCBF in normal state, and improve stability of rCBF in ischemic state. In addition, the present author also suggest that related mechanisms are involved in guanylate cyclase pathway.

• Journal of Acupuncture Research
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• v.28 no.4
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• pp.19-35
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• 2011

Objectives : This study was designed to investigate the effects of acupuncturing $PC_8$ used perpendicular needling method determine the mechanism of action of acupuncturing $PC_8$ by measuring the changes of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats. Methods : This study also investigated the effects of acupuncturing $PC_8$ on the change of rCBF in cerebral ischemic rats, and revealed the mechanism of its action. In addition, the effects of acupuncturing $PC_8$ on focal ischemic brain injury was studied in cerebral ischemic rats. Results : 1. Acupuncturing $PC_8$ significantly increase rCBF but decreased MABP in normal rats. 2. Acupuncturing $PC_8$ increased of rCBF was significantly inhibited by pretreatment with indomethacin (1mg/kg, i.p.), an inhibitor of cyclooxygenase in normal rats. 3. Acupuncturing $PC_8$ increased of rCBF was significantly inhibited by pretreatment methylene blue (10 ${\mu}g$/kg, i.p.), an inhibitor of guanylate cyclase in normal rats. 4. Acupuncturing $PC_8$ was significantly improved the rCBF than control group increased unstable in cerebral ischemic rats. 5. Acupuncturing $PC_8$ was not significantly improved the rCBF than control group by pretreatment with indomethacin (1mg/kg, i.p.), an inhibitor of cyclooxygenase in cerebral ischemic rats. 6. Acupuncturing $PC_8$ was significantly increased the rCBF than control group by pretreatment methylene blue ($10{\mu}g$/kg, i.p.), an inhibitor of guanylate cyclase in cerebral ischemic rats. Conclusions : In conclusion, our study suggested that acupuncturing $PC_8$ can increase rCBF in normal state, and improve stability of rCBF in ischemic state. In addition, we suggested that mechanisms related with acupuncturing $PC_8$ was involved in the guanylate cyclase pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.93-98
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• 2001

The precise mechanism of set-point regulation in hypothalamus was not elucidated. Nitric oxide synthases(NOS) were detected in hypothalamus, however, the roles of NO in hypothalamus was not fully studied. So, we tested the effects of NO on body temperature because preoptic-anterior hypothalamus was known as the presumptive primary fever-producing site. NO donor sodium nitroprusside (SNP, 4 nmol, i.c.v.) elicited marked febrile response, and this febrile response was completely blocked by indomethacin (a cyclooxygenase inhibitor). But, ODQ (selective guanylate cyclase inhibitor, $50\;{\mu}g,$ i.c.v.) did not inhibit fever induced by SNP. The cyclic GMP analogue dibutyryl-cGMP $(100\;{\mu}g,\;i.c.v.)$ induced significant pyreses, which is blocked by indomethacin. $N^G-nitro-L-arginine$ methyl ester (L-NAME, non selective NOS inhibitor) inhibited fever induced by $interleukin-1{\beta}\;(IL-1{\bata},\;10\;ng,\;i.c.v.),$ one of endogenous pyrogens. These results indicate that NO may have an important role, not related to stimulation of soluble guanylate cyclase, in the signal pathway of thermoregulation in hypothalamus.

• Nutrition Research and Practice
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• v.12 no.4
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• pp.291-297
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• 2018

BACKGROUND/OBJECTIVES: This study evaluated the effects and molecular mechanisms of the Schisandra chinensis fruit extract (SC) and its major compound gomisin A (GA), on the contractility of rabbit penile corpus cavernosum smooth muscle (PCCSM). MATERIALS/METHODS: PCCSM was exposed to SC or GA after appropriate pretreatment with nitric oxide synthase (NOS) blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker. Subsequently, we evaluated the cyclic nucleotide in the perfusate by radioimmunoassay, protein expression level of neuronal NOS (nNOS) and endothelial NOS (eNOS) by western blot, and the interaction of SC or GA with udenafil and rolipram. RESULTS: Both SC and GA induce PCCSM relaxations in a concentration-dependent manner. Pretreatment with NOS blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker result in significantly decreased relaxation. SC and GA also induce the levels of cyclic nucleotide in the perfusate in a concentration-dependent manner. Perfusion with GA also showed significantly higher levels of eNOS protein. Furthermore, the udenafil and rolipram induced relaxations of PCCSM were enhanced after exposure to SC and GA. Our results indicate that SC and GA induce the relaxation of PCCSM via the nitric oxide (NO)-cGMP and cAMP signaling pathways. CONCLUSIONS: The SC and GA are potential alternative treatments for men who want to consume natural products to ameliorate erectile function, or who do not respond to the commercially available medicines.

• Journal of Acupuncture Research
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• v.29 no.2
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• pp.73-88
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• 2012

Objectives : The purpose of this study is to research the effects of acupuncturing $BL_{67}$ and $LI_1$ and determine the mechanism of action of acupuncturing $BL_{67}$ and $LI_1$ by measuring the changes of regional cerebral blood flow(rCBF) and mean arterial blood pressure(MABP) in normal rats and ischemic rats. Method : This study researched the effects of acupuncturing $BL_{67}$ and $LI_1$ on the change of rCBF and MABP. To determine the mechanism of action of acupuncturing $BL_{67}$ and $LI_1$, pretreatment with indomethacine and methylene blue was done. Result : 1. Acupuncturing $BL_{67}$ and $LI_1$ significantly increased rCBF and acupuncturing $BL_{67}$ and $LI_1$ induced increase of rCBF was significantly inhibited by pretreatment with indomethacin(1 mg/kg, i.p.), an inhibitor of cyclooxygenase, and methylene blue(10 ${\mu}g$/kg, i.p.), an inhibitor of guanylate cyclase. 2. Acupuncturing $BL_{67}$ and $LI_1$ decreased MABP and there was no significantly change of decrease of MABP on acupuncturing $BL_{67}$ and $LI_1$ by pretreatment with indomethacin and methylene blue. 3. These result suggested that acupuncturing $BL_{67}$ and $LI_1$ might significantly increase rCBF by dilating arterial diameter and mechanism of acupuncturing $BL_{67}$ and $LI_1$ might be mediated by cyclooxygenase and guanylate cyclase. 4. The rCBF was significantly and stably increased by acupuncturing $BL_{67}$ and $LI_1$ during the period of cerebral reperfusion in cerebral ischemic rats, which contrasted with the rapid and marked increase in the control group. Pretreatment with methylene blue significantly decreased rCBF by acupuncturing $BL_{67}$ and $LI_1$ during the period of ischemic state, increased rCBF during the period of cerebral reperfusion. These results suggested that the mechanism of acupuncturing $BL_{67}$ and $LI_1$ might be mediated by guanylate cyclase. Conclusion : Acupuncturing $BL_{67}$ and $LI_1$ can increase rCBF in normal state, and improve stability of rCBF in ischemic state. In addition, we suggested that mechanisms related with acupuncturing $BL_{67}$ and $LI_1$ was more involved in the guanylate cyclase pathway.