• 동의생리병리학회지
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• 제20권1호
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• pp.181-186
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• 2006

A pharmacological inhibition of nitric oxide synthase (NOS) in rats produces vasoconstriction, renal dysfunction, and hypertension. The present study was aimed at investigating whether the methanol extract of Serous commixta cortex (MSC) ameliorates $N^G$-nitro-L-arginine methylester (L-NAME) induced hypertension in rats. Treatment of rats with L-NAME (10 mg/kg/day in drinking water, 5 weeks) caused a sustained increase in systolic blood pressure (SBP). Administration of MSC (100 or 200 mg/kg/day, p.o) significantly lowered the SBP in the L-NAME-treated rats and this effect was maintained throughout the whole experimental period. Moreover, ecNOS expression in aorta and kidney tissue from L-NAME treated rats was significantly restored dy administration of MSC. Furthermore, the impairment of acetylcholine (ACh)-induced relaxation of aortic rings in the L-NAME treated rats was reversed dy administering of MSC. The renal functional parameters including urinary volume, sodium excretion, and creatinine clearance (Ccr) were also restored by administering MSC. Taken together, the present study suggeststhat MSC prevents the increase in SBP in rats with L-NAME-induced hypertension, which may result from the up-regulation of the vascular and renal ecNOS/No system.

• 대한수의학회지
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• 제35권3호
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• pp.459-469
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• 1995

As S-nitrosothiols were proposed as nitrergic carriers in vascular and nonvascular smooth muscle, we have investigated the relaxant properties of several S-nitrosothiols in the porcine retractor penis(PRP) muscle and compared them with the effects of exogenously added NO, electrical field stimulation(EFS) of NANC nerves and sodium nitroprusside(SNP). Also the influences of oxyhemoglobin and hydroquinone on the relaxant responses were investigated. In addition, effects of NO on membrane potentials and its involvement in the generation of inhibitory junction potential(IJP) were investigated with conventional intracellular microelectrode technique. The results were summerized as follows. 1. Frequency-dependent relaxations of PRP muscle were induced by EFS to NANC nerve. Tetrodotoxin($1{\times}10^{-6}M$) abolished the relaxations of PRP muscle induced by EFS, and L-NAME(($2{\times}10^{-5}M$) and methylene blue($4{\times}10^{-5}M$) inhibited the relaxations. L-NAME-induced inhibition of the relaxations was reversed by L-arginine($1{\times}10^{-3}M$), but not by D-arginine. 2. Exogenous NO($1{\times}10^{-5}-1{\times}10^{-4}M$), sodium nitroprusside(($1{\times}10^{-7}-1{\times}10^{-4}M$) induced dose-dependent relaxations of PRP muscle. All S-nitrosothiols($1{\times}10^{-7}-1{\times}10^{-4}M$) tested relaxed the PRP muscle in dose-dependent manner and the potency order was SNAP>GSNO>CysNO>SNAC. 3. Oxyhemoglobin($5{\times}10^{-5}M$) blocked the relaxation induced by exogenous NO and inhibited EFS-, S-nitrosothiols-, and SNP-induced relaxation. 4. Hydroquinone($1{\times}10^{-4}M$) also abolished the relaxations induced by exogenous NO, and reduced the relaxations induced by S-nitrosothiols, but did not affect EFS- and SNP-induced relaxations. 5. SNP($2{\times}10^{-6}-5{\times}10^{-6}M$) relaxed muscle strips but the membrane potentials were not affected. 6. EFS with several pulses(1ms, 2Hz, 80V) produced an inhibitory junction potential(IJP) with muscle relaxation. They were abolished by TTX($2{\times}10^{-6}M$). $N^G$-nitro-$_{\small{L}}$-arginine(L-NNA, $2{\times}10^{-5}M$) abolished the muscle relaxation, but had no effect on IJP.

• Asian-Australasian Journal of Animal Sciences
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• 제24권9호
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• pp.1204-1210
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• 2011

Objective of this study was to examine the effect of sodium nitroprusside (SNP), a nitric oxide (NO) donor on steroid synthesis, growth and apoptosis of buffalo granulosa cells (GCs) in vitro. Follicular fluid of antral follicles (3-5 mm diameter) was aspirated and GCs were cultured in 0 (control), $10^{-3}$, $10^{-5}$, $10^{-7}$, $10^{-9}\;M$ of SNP for 48 h. To evaluate whether this effect was reversible, GCs were cultured in presence of $10^{-5}\;M$ SNP+1.0 mM $N^{\omega}$-nitro-L-arginine methyl ester (L-NAME) a NO synthase (NOS) inhibitor or hemoglobin (Hb, $1.0{\mu}g$) as NO scavenger. Nitrate/nitrite concentration was evaluated by Griess method, progesterone and estradiol concentrations by RIA and apoptosis by TUNEL assay. SNP ($10^{-3}$, $10^{-5}$, $10^{-7}\;M$) significantly (p<0.05) inhibited estradiol and progesterone synthesis, growth, disorganized GCs aggregates and induced apoptosis in a dose dependent manner. However, $10^{-9}\;M$ SNP induced the progesterone synthesis and stimulated GCs to develop into a uniform monolayer. Combination of SNP $10^{-5}$ M+L-NAME strengthened the inhibitory effect while, SNP+Hb together reversed these inhibitory effects. In conclusion, SNP at greater concentrations ($10^{-3}$, $10^{-5}$ and $10^{-7}\;M$) has a cytotoxic effect and it may lead to cell death whereas, at a lower concentration ($10^{-9}\;M$) induced progesterone synthesis and growth of GCs. These findings have important implications that NOS derived NO are involved at physiological level during growth and development of buffalo GCs which regulates the steroidogenesis, growth and apoptosis.

• Preventive Nutrition and Food Science
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• 제15권3호
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• pp.189-195
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• 2010

Water extracts from 20 medicinal plants, traditionally used for postmenopausal symptoms in Korea, were examined for their vasorelaxant activity in isolated rat thoracic aorta rings precontracted with norepinephrine (NE). Among the 20 medicinal plants, Cornus officinalis (CoEx, 0.3 mg/mL), Schisandra chinensis (ScEx, 0.3 mg/mL), Erythrina variegate (EvEx, 0.3 mg/mL), and Epimedium koreanum (EkEx, 0.3 mg/mL) showed rapid relaxation of endothelium-intact aorta ($69\pm4%$, $40\pm3%$, $25\pm2%$, and $23\pm3%$ of active tone induced by NE, respectively). In contrast, the extracts of Erythrina variegata (EvEx), Angelica gigas (AgEx), Pueraria thunbergiana (PtEx), and EkEx lead to gradual (i.e., long-term) relaxation to baseline in endothelium-intact vessels. The time to complete relaxation was 20～40 min. These 6 plant extracts were selected for the investigation of possible underlying mechanisms. The CoEx-, ScEx-, or EkEx-induced rapid relaxations were virtually abolished by endothelium denudation, and were significantly inhibited by pretreatment with nitric oxide (NO) synthase inhibitor $N^G$-nitro-L-arginine (L-NNA, 10 ${\mu}M$), indicating that increased formation of NO might contribute to the endothelium-mediated relaxation. In long-term responses, the endothelium denudation did not affect PtEx-induced relaxation, whereas it delayed responses by EvEx and AgEx, and significantly inhibited the effect of EkEx. Among EvEx, AgEx, and PtEx, EvEx attenuated the $CaCl_2$-induced vasoconstriction in high-potassium depolarized medium, implying that EvEx is involved in inhibition of the extracellular calcium influx to smooth muscle through voltage dependent calcium channels. These results provide the scientific rationale for the interrelationships between the use of 20 medicinal plants and their effects on cardiovascular health in estrogen deficient conditions.

• Advances in Traditional Medicine
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• 제2권2호
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• pp.87-93
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• 2002

The present study was aimed to examine the role of endothelium in the relaxant effect of hawthorn fruit extract of Crataegus pinnatifida in four different types of rat arteries, posterior cerebral communicating artery, right descending coronary artery, common carotid artery, and aorta. In $9,11-dideoxy-11{\alpha}$, $9{\alpha}-epoxy-methanoprostaglandin$ $F_{2{\alpha}}$ (U46619)-preconstricted arterial rings except for aorta, the extract produced endothelium-independent relaxations with similar potency. This relaxation was unaffected by pretreatment with $100\;{\mu}M\;N^G-nitro-L-arginine$ methylester (L-NAME, the nitric oxide synthase inhibitor), $3\;{\mu}M$ 1H-[l,2,4]oxadiazolo$[4,2-{\alpha}]$quinoxalin-1-one (ODQ, the guanylate cyclase inhibitor), or $10\;{\mu}M$ indomethacin (the cyclooxygenase inhibitor). Putative $K^+$ channel blockers (charybdotoxin plus apamin or glibenclamide) did not affect the extract-induced relaxation in cerebral or coronary artery rings. In contrast, in rat aortic rings the extract produced significantly smaller relaxant response in endothelium-denuded rings than that in endothelium-intact rings. Pretreatment with L-NAME or ODQ abolished the extractinduced endothelium-dependent aortic relaxation, whilst indomethacin $(3\;{\mu}M)$ had no effect. The present results indicate that hawthorn fruit extract possesses a vasorelaxing effect in cerebral, coronary and carotid arteries and this effect is independent of the presence of a functional endothelium. However, the extract-induced endothelium-dependent relaxation in rat aorta was mediated through endothelial nitric oxide and cyclic GMP-dependent mechanisms, suggesting that active components in the extract may act on endothelium to stimulate release of nitric oxide in large conduit arteries of the rats.

• 동의생리병리학회지
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• 제20권5호
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• pp.1166-1173
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• 2006

The aqueous extracts of Cortex Caryophylli (AEC) induced dose-dependent relaxation of phenylephrine-precontracted aorta, which was abolished by removal of functional endothelium. Pretreatment of the endothelium-intact aortic tissues with N$^G$_nitro-L-arginine methyl ester (L-NAME) or 1 H-[1,2,4]-oxadiazole-[4,3-${\alpha}$l-quinoxalin-1-one (ODQ) inhibited the relaxation induced by AEC. AEC-induced vascular relaxations were also markedly attenuated by addition of verapamil, diltiazem and glibenclamide, tetraethylammonium (TEA), respectively, while the relaxation effect of AEC was not blocked by indomethacin, atropine, or propranolol. Moreover, incubation of endothelium-intact aortic rings with AEC increased the production of cGMP. These results suggest that AEC dilates vascular smooth muscle via endothelium-dependent nitric oxide/cGMP signaling, which seems to be causally related with L-type Ca$^{2+}$ and K$^+$ channels.

• 한국균학회지
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• 제47권3호
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• pp.219-232
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• 2019

Chemicals related to hydrogen peroxide ($H_2O_2$) and nitric oxide (NO) generations were exogenously applied to Fusarium oxysporum f. sp. fragariae (Fof) causing Fusarium wilt disease in strawberry plants, and regulations of in vitro conidial germination and mycelial growth of the fungus by the chemical treatments were evaluated. $H_2O_2$ drastically reduced the conidial germination of Fof in a dose-dependent manner, and treatment with 3-amino-1,2,4-triazole (3-AT) catalase inhibitor also led to dose-dependent inhibition of conidial germination but relatively moderately. Gradual decreases in mycelial growth of Fof were found by high concentrations of $H_2O_2$, whilst exogenous 3-AT slightly increased the mycelial growth. Increasing sodium nitroprusside (SNP) NO donor, $N^G$-nitro-l-arginine methyl ester (L-NAME) NO synthase (NOS)-inhibitor and tungstate nitrate reductase (NR) inhibitor led to dose-dependent reductions in conidial germination of Fof in quite different levels. SNP conversely increased the mycelial growth but increasing L-NAME moderately decreased the mycelial growth. Tungstate strongly enhanced mycelial growth. Differentially regulated in vitro mycelial growths of Fof were demonstrated by SNP, L-NAME and tungstate with or without $H_2O_2$ supplement. Superoxide anion production was also regulated during the mycelial growth of Fof by nitric oxide. These results show that $H_2O_2$ and NO-associated enzymes can be suggested as fungal growth regulators of Fof as well as eco-friendly disease-managing agents in strawberry production fields.

• The Korean Journal of Physiology and Pharmacology
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• 제8권6호
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• pp.313-317
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• 2004

The present study were designed to characterize the action mechanisms of acetylcholine (ACh)-induced endothelium-dependent relaxation in arteries precontracted with high $K^+$(70 mM). For this, we simultaneously measured both muscle tension and cytosolic free $Ca^{2+}$ concentration $([Ca^{2+}]_i)$, using fura-2, in endothelium-intact, rabbit carotid arterial strips. In the artery with endothelium, high $K^+$ increased both $[Ca^{2+}]_i$ and muscle tension whereas ACh $(10{\mu}M)$ significantly relaxed the muscle and increased $[Ca^{2+}]_i$. In the presence of $N^G$-nitro-L-arginine (L-NAME, 0.1 mM), ACh increased $[Ca^{2+}]_i$ without relaxing the muscle. In the artery without endothelium, high $K^+$ increased both $[Ca^{2+}]_i$ and muscle tension although ACh was ineffective. 4-DAMP (10 nM) or atropine $(0.1{\mu}M)$ abolished ACh-induced increase in $[Ca^{2+}]_i$ and relaxation. The increase of $[Ca^{2+}]_i$ and vasorelaxation by ACh was siginificantly reduced by either $3{\mu}M$ gadolinium, $10{\mu}M$ lanthanum, or by $10{\mu}M$ SKF 96365. These results suggest that in rabbit carotid artery, ACh-evoked relaxation of 70 mM $K^+$-induced contractions appears to be mediated by the release of NO. ACh-evoked vasorelaxation is mediated via the $M_3$ subtype, and activation of the $M_3$ subtype is suggested to stimulate nonselective cation channels, leading to increase of $[Ca^{2+}]_i$ in endothelial cells.

• 생약학회지
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• 제37권2호통권145호
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• pp.67-73
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• 2006

The butanol extracts of Agrimonia pilosa (BAP) induced dose-dependent vascular relaxation of phenylephrine-precontracted aorta, which was abolished by removal of functional endothelium. Pretreatment of the endothelium-intact aortic tissues with $N^G$-nitro-L-arginine methyl ester (L-NAME) and 1H-[1,2,4]-oxadiazole-[$4,3-{\alpha}$]-quinoxalin-1-one(ODQ) inhibited the relaxation induced by BAP. BAP-induced vascular relaxation was also markedly attenuated by addition of verapamiI, while the relaxant effect of BAP was not blocked by indomethacine, glibenclamide, tetraethylammonium (TEA), atropine, or propranolo. In addition, incubation of endothelium-intact aortic rings with BAP increased the vascular production of cGMP. These results suggest that BAP relaxes vascular smooth muscle via endothelium-dependent nitric oxide/cGMP signaling pathway, which may be causally related with L-type $Ca^{2+}$ channels.

• 대한한의학방제학회지
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• 제17권2호
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• pp.175-186
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• 2009

The vasorelaxant effect of an extract of Lophatherum gracile Brongn (ELB) and its possible action mechanism were ascertained in aortic tissues isolated from rats. ELB relaxed endothelium-intact thoracic aorta in a dose-dependent manner. However, the induced vascular relaxation was abolished by removal in endothelium of the thoracic aorta. Pretreatment of endothelium-intact vascular tissues with $N^G$-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]-oxadiazole-[4,3-$\alpha$]-quinoxalin-1-one (ODQ) significantly inhibited vascular relaxation induced by ELB. Moreover, ELB significantly increased cGMP production in aortic tissues, which was blocked by pretreatment with L-NAME or ODQ. The vasorelaxant effect of ELB was attenuated by tetraethylammonium (TEA), and glibenclamide. ELB-induced vasorelaxation was not blocked by atropine, propranolol, indomethacin, verapamil, and diltiazem. Taken together, the present study demonstrates that ELB dilates vascular smooth muscle via an endothelium-dependent NO-cGMP signaling pathway, which may be at least in part related with the function of $K^+$ channels.