The Vasodilating Mechanism of Sodium Nitroprusside and Forskolin on Phorbol dibutyrate-Induced Contractions in Rat Aorta

안희열,Ahn, Hee-Yul The Korean Society of Pharmacology 1995 대한약리학잡지 Vol.31 No.3

The objectives of this study is to compare the inhibitory mechanism of sodium nitroprusside and forskolin on the phorbol ester, activator of protein kinase C (PKC), -induced contractions in rat aorta. $0.1\;{\mu}M$ phorbol dibutyrate (PDBu) induced sustained contractions and increased phosphorylations of myosin light chain (MLC) time-dependently. At 30 min, the contractions and phosphorylations of MLC by PDBu were augmented maximally and remained constant. Moreover, $^{45}Ca^{2+}$ uptake was increased 30 min after PDBu stimulation from resting values. Sodium nitroprusside which activates guanylyl cyclase followed by increasing cGMP, inhibited the PDBu-induced contractions concentration-dependently. On the other hand, forskolin which activates adenylyl cyclase followed by increasing cAMP, also inhibited the PDBu-induced contractions concentration-dependently. However, sodium nitroprusside was more potent to inhibition of the PDBu-induced contractions than forskolin. Sodium nitroprusside inhibited $^{45}Ca^{2+}$ uptake by PDBu stimulation. Forskolin also inhibited $^{45}Ca^{2+}$ uptake by PDBu stimulation. Sodium nitroprusside and forskolin inhibited the phosphorylations of MLC by PDBu, respectively. However, sodium nitroprusside was more potent to inhibition of phosphorylations of MLC by PDBu than forskolin. From these results, Sodium nitroprusside via cGMP or forskilin via cAMP may reduce myoplasmic $Ca^{2+}$ followed by suppression of phosphorylations of MLC of PKC-mediated contractions, which results in vasodilation. However, cGMP may play a role more importantly than cAMP on the regulation of protein kinase C-mediated contraction in vascular smooth muscle. 본 연구의 목적은 protein kinase C의 활성물질인 phorbol ester의 수축에 대한 cGMP 및 cAMP의 조절기전을 명확히 하기 위하여 흰쥐의 대동맥을 재료로 실험을 수행하였다. Sodium nitroprusside는 guanylyl cyclase를 활성화시켜 cGMP를, forskolin은 adenylyl cyclase를 활성화시켜서 cAMP를 증가시키는 것으로 보고되어 있으므로 위의 두 약물을 선택하였다. Phorbol ester는 시간경과와 함께 지속적인 수축을 발생하였으며 30분경 안정상태에 도달하였다. 동시에 20-kDa myosin light chain (MLC)의 인산화도 증가하였으며 30분경 최대치를 나타내었다. Sodium nitroprusside와 forskolin은 phorbol ester에 의한 수축을 농도의존적으로 억제하였으나 sodium nitroprusside가 forskolin보다 더욱 민감하게 억제하였다. Phorbol ester는 $^{45}Ca^{2+}$의 유입을 증가시켰고 sodium nitroprusside와 forskolin은 이 증가된 $^{45}Ca^{2+}$을 유의하게 억제하였다. Phorbol ester에 의하여 증가된 MLC의 인산화는 sodium nitroprusside 및 forskolin 각각의 최대농도로 억제되었다. 이상과 같은 결과로 볼때 아마도 cGMP와 cAMP는 phorbol ester에 의한 수축을 $^{45}Ca^{2+}$ 유입억제에 이은 MLC 인산화 억제에 의하여 이완작용을 나타내는 것으로 추측되며 cGMP가 cAMP보다 protein kinase C 매개의 수축조절에 더 중요하게 작용하리라 추측된다.

Sodium nitroprusside와 Forskolin의 Phorbol ester 수축에 대한 혈관이완작용의 기전

안희열(Hee Yul Ahn) 대한약리학회 1995 대한약리학잡지 Vol.31 No.3

본 연구의 목적은 protein kinase C의 활성물질인 phorbol ester의 수축에 대한 cGMP 및 cAMP의 조절기전을 명확히 하기 위하여 흰쥐의 대동맥을 재료로 실험을 수행하였다. Sodium nitroprusside는 guanylyl cyclase를 활성화시켜 cGMP를, forskolin은 adenylyl cyclase를 활성화시켜서 cAMP를 증가시키는 것으로 보고되어 있으므로 위의 두 약물을 선택하였다. Phorbol ester는 시간경과와 함께 지속적인 수축을 발생하였으며 30분경 안정상태에 도달하였다. 동시에 20-kDa myosin light chain (MLC)의 인산화도 증가하였으며 30분경 최대치를 나타내었다. Sodium nitroprusside와 forskolin은 phorbol ester에 의한 수축을 농도의존적으로 억제하였으나 sodium nitroprusside가 forskolin보다 더욱 민감하게 억제하였다. Phorbol ester는 ⁴⁵Ca²⁺의 유입을 증가시켰고 sodium nitroprusside와 forskolin은 이 증가된 ⁴⁵Ca²⁺을 유의하게 억제하였다. Phorbol ester에 의하여 증가된 MLC의 인산화는 sodium nitroprusside 및 forskolin 각각의 최대농도로 억제되었다. 이상과 같은 결과로 볼때 아마도 cGMP와 cAMP는 phorbol ester에 의한 수축을 ⁴⁵Ca²⁺ 유입억제에 이은 MLC 인산화 억제에 의하여 이완작용을 나타내는 것으로 추측되며 cGMP가 cAMP보다 protein kinase C 매개의 수축조절에 더 중요하게 작용하리라 추측된다. The objectives of this study is to compare the inhibitory mechanism of sodium nitroprusside and forskolin on the phorbol ester, activator of protein kinase C (PKC), -induced contractions in rat aorta. 0.1μM phorbol dibutyrate (PDBu) induced sustained contractions and increased phosphorylations of myosin light chain (MLC) time-dependently. At 30 min, the contractions and phosphorylations of MLC by PDBu were augmented maximally and remained constant. Moreover, ⁴⁵Ca²⁺ uptake was increased 30 min after PDBu stimulation from resting values. Sodium nitroprusside which activates guanylyl cyclase followed by increasing cGMP, inhibited the PDBu-induced contractions concentration-dependently. On the other hand, forskolin which activates adenylyl cyclase followed by increasing cAMP, also inhibited the PDBu-induced contractions concentration-dependently. However, sodium nitroprusside was more potent to inhibition of the PDBu-induced contractions than forskolin. Sodium nitroprusside inhibited ⁴⁵Ca²⁺ uptake by PDBu stimulation. Forskolin also inhibited ⁴⁵Ca²⁺ uptake by PDBu stimulation. Sodium nitroprusside and forskolin inhibited the phosphorylations of MLC by PDBu, respectively. However, sodium nitroprusside was more potent to inhibition of phosphorylations of MLC by PDBu than forskolin. From these results, Sodium nitroprusside via cGMP or forskilin via cAMP may reduce myoplasmic Ca²⁺ followed by suppression of phosphorylations of MLC of PKC-mediated contractions, which results in vasodilation. However, cGMP may play a role more importantly than cAMP on the regulation of protein kinase C-mediated contraction in vascular smooth muscle.

저 산소/재산소화와 Sodium Nitroprusside가 분리 위선세포의 산 분비 및 세포 내 Cyclic Nucleotide에 미치는 영향

김혜영,이송철,김경환 大韓消化器病學會 1997 大韓消化器病學會誌 Vol.29 No.2

Effect of Pancreatic Polypeptide Family on Cardiovascular Muscle Contractility: 1. Interactions with cyclic nucleotide activators and $K^+$ channel openers in canine cerebral arteries

김원준,이광윤,하정희,권오철,Kim, Won-Joon,Lee, Kwang-Youn,Ha, Jeoung-Hee,Kwon, Oh-Cheol The Korean Society of Pharmacology 1992 대한약리학잡지 Vol.28 No.2

Pancreatic polypeptide family펩타이드들의 뇌혈관 평활근 수축성에 미치는 효과를 관찰하고, cyclic nucleotide 활성제 및 칼륨통로개방제와의 상호작용을 관찰하기 위하여 다음과 같은 실험을 하였다. 체중 $20{\sim}30\;g$의 개를 사혈 희생시켜 두개골을 절개한 후 뇌저동맥과 중뇌동맥을 적출하였다. 적출된 동맥편은 $4^{\circ}C$의 생리적식염수 내에서 나선형 절편으로 만들어 0.3%의 CHAPS 용액에 침잠시킴으로써 내피세포층을 제거한 후 95% $O_2$와 5% $CO_2$의 혼합기체로 포화된 $37^{\circ}C$의 Krebs-Henseleit 용액을 포함한 적출근편실험조에서 등척성 장력을 측정하였다. 1. PP, PYY 및 NPY는 뇌동맥 나선형절편을 농도의존적으로 수축시켰으며, 그 효력과 효능은 PYY가 가장 강하였고, 그 다음이 NPY, 그리고 PP의 순이었다. 이들의 효력은 노르아드레날린보다 20내지 200배 강하였으며, 그 중 PYY는 5-HT 보다도 강한 효력을 보였다. 2. Cyclic AMP 활성제인 forskolin과 cyclic GMP 활성제인 sodium nitroprusside는 뇌동맥절편의 기본장력을 감소시켰으며, PP, PYY 및 NPY 유발수축 역시 농도의존적으로 억제하였다. 이 때 forskolin의 기본장력억제작용이 sodium nitroprusside보다 강한 효력을 나타내었다. 3. 칼륨통로 개방제인 RP 49356, P 1060 및 BRL 38227은 기본장력에 대해서는 공히 농도의존적으로 억제하였으나, PP, PYY 및 NPY 유발수축에 대해서는 P 1060만이 농도의존적으로 억제하였고, RP 49356 및 BRL 38227은 약간 억제하는 경향만을 보였는데, 특기할 것은 저농도의$(0.1\;{\mu}M)$ BRL 38227이 이들 펩타이드 유발수축을 오히려 증가 시켰다는 것이다. 4. 기본장력에 대해서, 칼륨통로개방제들은 forskolin의 이완작용에 유의한 영향을 미치지 못하였으나, 그중 P 1060과 BRL 38227은 sodium nitroprusside의 이완작용을 상승적으로 강화하였다. PYY$(0.1\;{\mu}M)$유발 수축작용에 대해서, 칼륨통로 개방제들은 forskolin의 수축억제작용에 대해서는 약간 길항하는 경향만을 보였고, sodium nitroprusside의 수축억제작용은 유의하게 길항하였다. 이상의 결과들을 종합하면, 개의 뇌혈관에서는 NPY 뿐만 아니라 PYY도 혈관수축기전에 중요한 역할을 한다고 볼 수 있으며, 그 수축작용의 기전에는 세포내 cAMP 및 cGMP 활성도의 변화가 포함된다고 사료된다. 또 칼륨통로개방제들은 pancreatic polypeptide family의 뇌혈관수축작용에 대하여 제제 및 농도에 따라 다양한 영향을 미치므로 이에 대한 향후의 더욱 세밀한 연구가 요구된다. The objectives of the present experiments were to characterize the effects of the peptides belonging to the pancreatic polypeptide family on the contractility of cerebral arteries and to observe the interactions of these peptides with the cyclic nucleotide activators and the potassium channel openers. Dogs of either sex, $20{\sim}30\;Kg$ in weight, were sacrificed. Basilar and middle cerebral arteries from brain were isolated and prepared for myography in the PSS equilibrated with 95% $O_2$ and 5% $CO_2$ at $37^{\circ}C$. The endothelial cells of the spiral strips were removed by CHAPS solution (0.3% w/v, 15 seconds). 1. PP, PYY and NPY contracted the arterial strips concentration-dependently with a rank order of potency of PYY>NPY>PP. These peptides were 20 to 200 times more potent than norepinephrine, and only PYY showed a greater potency than 5-HT. 2. Cyclic nucleotide activators, forskolin (for cAMP) and sodium nitroprusside (for cGMP) reduced the basal tone and inhibited the PP-, PYY- and NPY- induced contractions by concentration-dependent manners. Forskolin was more potent in reducing basal tone than sodium nitroprusside. 3. Potassium channel openers, RP 49356, P 1060 and BRL 38227 reduced the basal tone concentration-dependently and tended to inhibit the PP-, PYY- and NPY- induced contractions. Notably, BRL 38227 with low concentration $(0.1\;{\mu}M)$ enhanced the contractions induced by those peptides while P 1060 inhibited the contractions concentration-dependently. 4. The combinations of the cyclic nucleotide activators and the potassium channel openers were slightly additive in reducing the basal tone. P 1060 and BRL 38227 enhanced the relaxant effect of sodium nitroprusside significantly. On the PYY-induced contration $(0.1\;{\mu}M)$, $K^+$ channel openers tended to inhibit the inhibitory actions of forskolin and sodium nitroprusside. P 1060 and BRL 38227 antagonized the inhibitory action of sodium nitroprusside significantly. The results of the present study may be summarized that in canine cerebral arteries, not only NPY but also PYY may play a role in a cerebrovascular spasm, and intracellular concentration of either cAMP or cGMP may be involved in the mechanism of vasoconstrictive actions of these peptides, which may be affected either positively or negatively by a $K^+$ channel opener.

Pancreatic Polypeptide Family의 심혈관계 근육 수축성에 대한 약리학적 작용: I. 개의 뇌혈관에서 cyclic nucleotide활성제와 칼륨통로개방제와의 상호작용

김원준(Won Joon Kim),이광윤(Kwang Youn Lee),하정희(Jeoung Hee Ha),권오철(Oh Cheol Kwon) 대한약리학회 1992 대한약리학잡지 Vol.28 No.2

Pancreatic polypeptide family펩타이드들의 뇌혈관 평활근 수축성에 미치는 효과를 관찰하고, cyclic nucleotide 활성제 및 칼륨통로개방제와의 상호작용을 관찰하기 위하여 다음과 같은 실험을 하였다. 체중 20 ~ 30 g의 개를 사혈 희생시켜 두개골을 절개한 후 뇌저동맥과 중뇌동맥을 적출하였다. 적출된 동맥편은 4˚C의 생리적식염수 내에서 나선형 절편으로 만들어 0.3%의 CHAPS 용액에 침잠시킴으로써 내피세포층을 제거한 후 95% O<Sub>2</sub>와 5% CO₂의 혼합기체로 포화된 37˚C의 Krebs-Henseleit 용액을 포함한 적출근편실험조에서 등척성 장력을 측정하였다. 1. PP, PYY 및 NPY는 뇌동맥 나선형절편을 농도의존적으로 수축시켰으며, 그 효력과 효능은 PYY가 가장 강하였고, 그 다음이 NPY, 그리고 PP의 순이었다. 이들의 효력은 노르아드레날린보다 20내지 200배 강하였으며, 그 중 PYY는 5-HT 보다도 강한 효력을 보였다. 2. Cyclic AMP 활성제인 forskolin과 cyclic GMP 활성제인 sodium nitroprusside는 뇌동맥절편의 기본장력을 감소시켰으며, PP, PYY 및 NPY 유발수축 역시 농도의존적으로 억제하였다. 이 때 forskolin의 기본장력억제작용이 sodium nitroprusside보다 강한 효력을 나타내었다. 3. 칼륨통로 개방제인 RP 49356, P 1060 및 BRL 38227은 기본장력에 대해서는 공히 농도의존적으로 억제하였으나, PP, PYY 및 NPY 유발수축에 대해서는 P 1060만이 농도의존적으로 억제하였고, RP 49356 및 BRL 38227은 약간 억제하는 경향만을 보였는데, 특기할 것은 저농도의(0.1μM) BRL 38227이 이들 펩타이드 유발수축을 오히려 증가 시켰다는 것이다. 4. 기본장력에 대해서, 칼륨통로개방제들은 forskolin의 이완작용에 유의한 영향을 미치지 못하였으나, 그중 P 1060과 BRL 38227은 sodium nitroprusside의 이완작용을 상승적으로 강화하였다. PYY(0.1μM)유발 수축작용에 대해서, 칼륨통로 개방제들은 forskolin의 수축억제작용에 대해서는 약간 길항하는 경향만을 보였고, sodium nitroprusside의 수축억제작용은 유의하게 길항하였다. 이상의 결과들을 종합하면, 개의 뇌혈관에서는 NPY 뿐만 아니라 PYY도 혈관수축기전에 중요한 역할을 한다고 볼 수 있으며, 그 수축작용의 기전에는 세포내 cAMP 및 cGMP 활성도의 변화가 포함된다고 사료된다. 또 칼륨통로개방제들은 pancreatic polypeptide family의 뇌혈관수축작용에 대하여 제제 및 농도에 따라 다양한 영향을 미치므로 이에 대한 향후의 더욱 세밀한 연구가 요구된다. The objectives of the present experiments were to characterize the effects of the peptides belonging to the pancreatic polypeptide family on the contractility of cerebral arteries and to observe the interactions of these peptides with the cyclic nucleotide activators and the potassium channel openers. Dogs of either sex, 20 ~ 30 Kg in weight, were sacrificed. Basilar and middle cerebral arteries from brain were isolated and prepared for myography in the PSS equilibrated with 95% O<Sub>2</sub> and 5% CO₂ at 37˚C. The endothelial cells of the spiral strips were removed by CHAPS solution (0.3% w/v, 15 seconds). 1. PP, PYY and NPY contracted the arterial strips concentration-dependently with a rank order of potency of PYY>NPY>PP. These peptides were 20 to 200 times more potent than norepinephrine, and only PYY showed a greater potency than 5-HT. 2. Cyclic nucleotide activators, forskolin (for cAMP) and sodium nitroprusside (for cGMP) reduced the basal tone and inhibited the PP-, PYY- and NPY- induced contractions by concentration-dependent manners. Forskolin was more potent in reducing basal tone than sodium nitroprusside. 3. Potassium channel openers, RP 49356, P 1060 and BRL 38227 reduced the basal tone concentration-dependently and tended to inhibit the PP-, PYY- and NPY- induced contractions. Notably, BRL 38227 with low concentration (0.1μM) enhanced the contractions induced by those peptides while P 1060 inhibited the contractions concentration-dependently. 4. The combinations of the cyclic nucleotide activators and the potassium channel openers were slightly additive in reducing the basal tone. P 1060 and BRL 38227 enhanced the relaxant effect of sodium nitroprusside significantly. On the PYY-induced contration (0.1μM), K⁺ channel openers tended to inhibit the inhibitory actions of forskolin and sodium nitroprusside. P 1060 and BRL 38227 antagonized the inhibitory action of sodium nitroprusside significantly. The results of the present study may be summarized that in canine cerebral arteries, not only NPY but also PYY may play a role in a cerebrovascular spasm, and intracellular concentration of either cAMP or cGMP may be involved in the mechanism of vasoconstrictive actions of these peptides, which may be affected either positively or negatively by a K⁺ channel opener.

Phenylephrine에 의한 수축에 대한 Sodium Nitroprusside의 혈관수축 증대효과

제현동(Hyun Dong Je) 대한약학회 2006 약학회지 Vol.50 No.3

Rat aortic ring preparations were mounted in organ baths, exposed to sodium cyanide (0.01~1.0mM) for 10min, and then subjected to contractile agents or relaxants such as acetylcholine, sodium nitroprusside and isoproterenol. Presence of low concentration of sodium cyanide did not affect the contractile response to KCl or phenylephrine in the aortic rings with intact endothelium or endothelium denuded. Sodium nitroprusside but not acetylcholine or isoproterenol augmented phenylephrine-induced intact or denuded vascular contraction in the presence of low concentration of sodium cyanide. In conclusion, this study provides the evidence concerning the potentiating effect of sodium nitroprusside on the contraction induced by phenylephrine in rat aortic rings regardless of endothelial function.

Sodium Nitroprusside와 Prostaglandin E1을 이용한 유도저혈압이 압수용체반사에 미치는 영향

김학식,강건,김익동,김인세,정규섭 해성병원 1992 海星病院論文集 Vol.1 No.-

Hot Pepper (Capsicum spp.) Protects Brain from Sodium Nitroprusside- and Quinolinic Acid-Induced Oxidative Stress In Vitro

G. Oboh,J.B.T. Rocha 한국식품영양과학회 2008 Journal of medicinal food Vol.11 No.2

One practical way through which free radical-mediated neurodegenerative diseases could be prevented isthrough the consumption of food rich in antioxidants. The ability of aqueous extracts of ripe and unripe Capsicum annum,Tepin (CAT) and Capsicum chinese, Habanero (CCH) to prevent lipid peroxidation induced by sodium nitroprusside andquinolinic acid in rat brain in vitrois assessed in this study. The aqueous extract of the peppers were prepared (1 g/20 mL).Incubating rat brain homogenates with pro-oxidant (7 .M sodium nitroprusside [222.5%] and 1 mM quinolinic acid [217.4%])caused a significant increase (P. .05) in lipid peroxidation in rat brain homogenates. However, the aqueous extract of thepeppers (4.216.8 mg/mL) caused a significant decrease (P. .05) in the lipid peroxidation in a dose-dependent manner. How-ever, unripe CAT (92.555.2%) caused the highest inhibition of sodium nitroprusside-induced lipid peroxidation, while un-ripe CCH caused the least inhibition (161.0102.1%). Furthermore, unripe CAT and CCH peppers had a significantly higher(P. .05) inhibitory effect on quinolinic acid-induced lipid peroxidation in rat brain than the ripe pepper (CAT and CCH).Therefore, the protection of the brain tissues by hot pepper depends on the total phenol content in sodium nitroprusside-in-duced lipid peroxidation, while ripening would reduce the protective properties of hot pepper against quinolinic acid-inducedlipid peroxidation. However, unripe CAT has the highest protective properties against sodium nitroprusside- and quinolinicacid-induced lipid peroxidation in rat brain.

EFFECTS OF SODIUM NITROPRUSSIDE ON THE FORMATION AND ACTIVATION OF THE OSTEOCLAST IN CULTURE

Yoo, Young-Jae,Kim, Jung-Kun,Cha, Kyung-Suk 대한치과교정학회 1995 대한치과교정학회지 Vol.25 No.6

Due to the great deal of effort that has gone into the study of osteoclastic differentiation and activation over the last few decades, the mechanisms of these two events have been discovered gradually. Nitric oxide(NO^-), which is produced from arginine by a nitric oxide synthase, opened up a new area of bilogical research. Recently, it has been reported that NO^- is produced by osteoblasts stimulated by lipopolysaccharide and several other cytokines. In this study, the effect of sodium nitroprusside(SNP), a donor of nitric oxide(NO^-), on osteoclast-like cell formation and on mature osteoclast function was examined. To determine the mechanism of the inhibitory effects of SNP decreased not only the basal ^45Ca release but also thee bone resorption induced by PTH and 1,25-digydroxyvitamin D_3 (1,25[OH]_2D_3). The inhibitory effect of SNP on bone resorption induced by 1,25[OH]_2D_3 appeared at the thhird days. When chicken and rat osteeoclasts were cultured on dentin slices, treatment of 300 γM SNP resulted in a significant decrease in dentin resorption by osteoclasts in terms of total resorption area and average individual area. We also examind the effect of SNP on formation of osteoclasts-like cells that is TRP-positive multinucleated cells from chicken and rat bone marrow cells in the presence of absence of 10_8 M 1,25[OH]_2D_3. The addition of 300 γ M SNP inhibiteed the formation of TRAP-positive multinucleated cells. The present data suggest that SNP, possibly as a NO^- donor, inhibits the osteoclastic differentiation and osteoclastic activity.

기니 픽 장관 평활근에서 Sodium Nitroprusside가 장력에 미치는 영향

권성춘,김시연,김은주,강복순,Kwon, Seong-Chun,Kim, Si-Yeon,Kim, Eun-Ju,Kang, Bok-Soon 대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.6

Nitric oxide (NO) has been 3mown as a mediator of nonadrenergic, noncholinergic inhibitory neurotransmitter in intestinal smooth muscles. It has been suggested that NO donor such as sodium nitroprusside (SNP) produces relaxation of smooth muscle via activation of guanylate cyclase and elevation of cGMP levels. We have therefore investigated the effects of NO, using SNP, on muscle tension in the longitudinal smooth muscle of guinea-pig ileum. The possible role of cGMP was also investigated as well as the involvement of $K^+$ channel on SNP-induced inhibitory effect. The results are summarized as follows; high KCI-or CCh-activated contractions were inhibited by SNP in a concentration-dependent manner. 8-Br-cGMP also showed a similar effect in that of SNP TEA (1 mM) significantly reduced the SNP-induced inhibitory effect. SNP-induced effect was forther reduced by the presence of 10 mM TEA. On the other hand, 4-AP (0.1 mM), glibenclamide $(10\;{\mu}M)$ and apinain $(0.1\;{\mu}M)$ showed little effects on SNP-induced relaxation. Zaprinast significantly potentiated the SNP-induced inhibitory effect in all ranges. ODQ also significantly decreased the SNP-induced inhibitory effect. Pretreatment with CPA $(10\;{\mu}M)$ slightly reduced the SNP-induced inhibitory effect. From the above results, both effect mediated by NO and cGMP might be responsible for the activation of $Ca^{2+}$-activated $K^+$ channel by SNP in guinea-rig ileum. And this $K^+$ channel activation by SNP also contributes to the SNP-induced membrane hyperpolarization and relaxation.