Faculty Profiles - ZAMAMI Yoshito

岡山大学病院高度救急救命センターにおける抗MRSA薬TDMへの継続的関与の有用性

座間味義人, 名倉弘哲, 武本あかね, 森定淳, 木浪陽, 山内英雄, 寺戸通久, 鵜川豊世武, 市場晋吾, 氏家良人

日本臨床救急医学会雑誌 16 ( 3 ) 407 - 407 2013.6

切除不能な進行・再発の直腸・結腸がん3次治療におけるセツキシマブとパニツムマブの費用対効果分析

永尾香菜子, 小林明日香, 座間味義人, 名和秀起, 野間和広, 五十嵐中, 千堂年昭, 名倉弘哲

日本薬学会年会要旨集 133年会 ( 3 ) 245 - 245 2013.3

塩酸デクスメデトミジン投与患者におけるせん妄発症の危険因子解析

名倉弘哲, 藤原歩, 座間味義人, 鵜川豊世武, 氏家良人

日本臨床医学リスクマネジメント学会・学術集会プログラム・抄録集 11回 81 - 81 2013.3

岡山大学病院高度救命救急センターにおける薬剤経管投与方法への薬剤師の介入症例

座間味義人, 名倉弘哲, 飯田淳義, 塚原紘平, 寺戸通久, 鵜川豊世武, 芝直基, 山内英雄, 市場晋吾, 氏家良人

日本集中治療医学会雑誌 20 ( Suppl. ) 413 - 413 2013.1

岡山大学病院高度救命救急センターへの全国初となる救急薬学講座参入

名倉弘哲, 座間味義人, 寺戸通久, 芝直基, 平山敬浩, 森定淳, 山内英雄, 鵜川豊世武, 市場晋吾, 氏家良人

日本集中治療医学会雑誌 20 ( Suppl. ) 442 - 442 2013.1

Do cholinergic nerves innervating rat mesenteric arteries regulate vascular tone? Reviewed

Panot Tangsucharit, Shingo Takatori, Pengyuan Sun, Yoshito Zamami, Mitsuhiro Goda, Poungrat Pakdeechote, Fusako Takayama, Hiromu Kawasaki

AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY 303 ( 11 ) R1147 - R1156 2012.12

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER PHYSIOLOGICAL SOC

Tangsucharit P, Takatori S, Sun P, Zamami Y, Goda M, Pakdeechote P, Takayama F, Kawasaki H. Do cholinergic nerves innervating rat mesenteric arteries regulate vascular tone? Am J Physiol Regul Integr Comp Physiol 303: R1147-R1156, 2012. First published October 10, 2012; doi:10.1152/ajpregu.00317.2012.-Vascular blood vessels have various types of cholinergic acetylcholine receptors (AChR), but the source of ACh has not been confirmed. Perivascular adrenergic nerves and nonadrenergic calcitonin gene-related peptide (CGRP)-containing (CGRPergic) nerves innervate rat mesenteric arteries and regulate vascular tone. However, function of cholinergic innervation remains unknown. The present study investigated cholinergic innervation by examining effects of cholinesterase inhibitor (neostigmine), a muscarinic AChR antagonist (atropine), and a nicotinic AChR antagonist (hexamethonium) on adrenergic nerve-mediated vasoconstriction and CGRPergic nerve-mediated vasodilation in rat mesenteric vascular beds without endothelium. In preparations treated with capsaicin (CGRP depletor) or in the presence of N-omega-nitro-L-arginine methyl ester (nonselective nitric oxide synthase inhibitor), perivascular nerve stimulation (PNS; 2-12 Hz) evoked a frequency-dependent vasoconstriction. In the same preparations, exogenous norepinephrine induced a concentration-dependent vasoconstriction. Atropine, hexamethonium, and neostigmine had no effect on vasoconstrictor responses to PNS and norepinephrine injections. In denuded preparations, these cholinergic agents did not affect the PNS (12 Hz)-evoked release of norepinephrine in perfusate. In preconstricted preparations without endothelium in the presence of guanethidine (adrenergic neuron blocker), PNS (1-4 Hz) induced a frequency-dependent vasodilation, which was not affected by atropine, hexamethonium, and neostigmine. In denuded preparations treated with capsaicin and guanethidine, PNS did not induce vascular responses, and atropine, neostigmine, and physostigmine had no effect on PNS. Immunohistochemistry study showed choline acetyltransferase-immunopositive fibers, which were resistant to capsaicin and 6-hydroxy-dopamine (adrenergic toxin). These results suggest that rat mesenteric arteries have cholinergic innervation, which is different from adrenergic and capsaicin-sensitive nerves and not associated with vascular tone regulation.

DOI： 10.1152/ajpregu.00317.2012

Quinolone Analogues 12: Synthesis and Tautomers of 2-Substituted 4-Quinolones and Related Compounds Reviewed

Yoshihisa Kurasawa, Kiminari Yoshida, Naoki Yamazaki, Kotoji Iwamoto, Yoshihiko Hamamoto, Eisuke Kaji, Kenji Sasaki, Yoshito Zamami

JOURNAL OF HETEROCYCLIC CHEMISTRY 49 ( 6 ) 1323 - 1331 2012.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

The 4-quinolone-2-carboxylates 4a,b were converted into the 4-quinolone-2-carbohydrazides 5a,b, hydrazones 6,7,10, and related compounds 8,9,11. The 4-methoxyquinoline-2-carboxylate 12 was also transformed into the 4-methoxyquinoline-2-carbohydrazide 13, which was modified to the hydrazone 14 and related compound 15. The antimicrobial activities of compounds 6b and 14 are described together with the 4-oxo and 4-hydroxy tautomers of compounds 4-11 in deuteriodimethyl sulfoxide and deuteriotrifluoroacetic acid.

DOI： 10.1002/jhet.922

Scopus

岡山大学薬学部救急薬学分野の発足全国初の救急薬学

名倉弘哲, 武本あかね, 座間味義人, 寺戸通久, 芝直基, 飯田淳義, 木浪陽, 山内英雄, 鵜川豊世武, 市場晋吾, 氏家良人

日本救急医学会雑誌 23 ( 10 ) 679 - 679 2012.10

Pharmacist-Physical Assessment Lab(P-PAL)活動報告岡山大学大学院救急薬学分野との共催による卒後薬剤師教育について

立野朋志, 名倉弘哲, 座間味義人, 尾上洋, 堀淵浩二, 松永るみ

日本薬剤師会学術大会講演要旨集 45回 204 - 204 2012.10

Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries Reviewed

Hirohito Fujii, Shingo Takatori, Yoshito Zamami, Narumi Hashikawa-Hobara, Natsuki Miyake, Panot Tangsucharit, Mitsunobu Mio, Hiromu Kawasaki

BRITISH JOURNAL OF PHARMACOLOGY 166 ( 7 ) 2084 - 2094 2012.8

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

BACKGROUND AND PURPOSE 5-HT is taken up by and stored in adrenergic nerves and periarterial nerve stimulation (PNS) releases 5-HT to cause vasoconstriction in rat mesenteric arteries. The present study investigated whether PNS-released 5-HT stored in adrenergic nerves affects the function of perivascular calcitonin gene-related peptide-containing (CGRPergic) nerves. EXPERIMENTAL APPROACH Rat mesenteric vascular beds without endothelium and with active tone were perfused with Krebs solution. Changes in perfusion pressure in response to PNS and CGRP injection were measured before (control) and after perfusion of Krebs solution containing 5-HT (10 mu M) for 20 min. Distributions of 5-HT- and TH-immunopositive fibres in mesenteric arteries were studied using immunohistochemical methods. KEY RESULTS PNS (14 Hz) frequency dependently caused adrenergic nerve-mediated vasoconstriction followed by CGRPergic nerve-mediated vasodilatation. 5-HT treatment inhibited PNS-induced vasodilatation without affecting exogenous CGRP-induced vasodilatation, while it augmented PNS-induced vasoconstriction. Guanethidine (adrenergic neuron blocker), methysergide (non-selective 5-HT receptor antagonist) and BRL15572 (selective 5-HT1D receptor antagonist) abolished inhibition of PNS-induced vasodilatation in 5-HT-treated preparations. Combined treatment with 5-HT and desipramine (catecholamine transporter inhibitor), but not fluoxetine (selective 5-HT reuptake inhibitor), did not inhibit PNS-induced vasodilatation. Exogenous 5-HT inhibited PNS-induced vasodilatation, which was antagonized by methysergide. In immunohistochemical experiments, 5-HT-immunopositive nerves, colocalized with adrenergic TH-immunopositive nerves, were observed only in 5-HT-treated mesenteric arteries, but not in control preparations or arteries co-treated with desipramine. CONCLUSIONS AND IMPLICATIONS These results suggest that 5-HT can be taken up by and released from adrenergic nerves in vitro by PNS to inhibit CGRPergic nerve transmission in rat mesenteric arteries.

DOI： 10.1111/j.1476-5381.2012.01935.x

Synthesis and antimalarial activity of calothrixins A and B, and their N-alkyl derivatives Reviewed

Kohji Matsumoto, Tominari Choshi, Mai Hourai, Yoshito Zamami, Kenji Sasaki, Takumi Abe, Minoru Ishikura, Noriyuki Hatae, Tatsunori Iwamura, Shigeo Tohyama, Junko Nobuhiro, Satoshi Hibino

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 22 ( 14 ) 4762 - 4764 2012.7

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

We synthesized calothrixin B using our developed biomimetic method and derived N-alkyl-calothrixins A and B. The in vitro antimalarial activity of the calothrixin derivatives, including calothrixins A and B, against the Plasmodium falciparum FCR-3 strain was evaluated. All test compounds exhibited antimalarial activity over a concentration range of 6.4 x 10(-6)-1.2 x 10(-7) M. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmcl.2012.05.064

Neurogenic Vascular Responses in Male Mouse Mesenteric Vascular Beds Reviewed

Hiroki Fujiwara, Narumi Hashikawa-Hobara, Yoshihiro Wake, Shingo Takatori, Mitsuhiro Goda, Hiroshi Higuchi, Yoshito Zamami, Panot Tangsucharit, Hiromu Kawasaki

JOURNAL OF PHARMACOLOGICAL SCIENCES 119 ( 3 ) 260 - 270 2012.7

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE PHARMACOLOGICAL SOC

Rat mesenteric arteries were maintained by both adrenergic vasoconstrictor nerves and calcitonin gene related peptide (CGRP) vasodilator nerves. However, functions of these nerves in a pathophysiological state have not fully been analyzed. The use of disease models developed genetically in mice is expected to clarify neural function of perivascular nerves. Thus, we investigated basic mouse vascular responses. Mesenteric vascular beds isolated from male C57BL/6 mouse were perfused with Krebs solution and perfusion pressure was measured. Periarterial nerve stimulation (PNS, 8 - 24 Hz) induced frequency-dependent vasoconstriction, which increased flow rate dependently. PNS-induced vasoconstriction was abolished by tetrodotoxin (neurotoxin) and guanethidine (adrenergic neuron blocker) and blunted by prazosin (alpha(1)-adrenoceptor antagonist). Injection of norepinephrine caused vasoconstriction, which was abolished by prazosin. In preparations with active tone, PNS (1 - 8 Hz) induced frequency-dependent vasodilation, which was inhibited by tetrodotoxin, capsaicin (CGRP depletor), and CGRP8-37 (CGRP-receptor antagonist). Injections of CGRP, acetylcholine, and sodium nitroprusside induced vasodilations. Vasodilator response to CGRP was inhibited by CGRP8-37. Immunohistochemical study showed innervation of tyrosine hydroxylase- and CGRP-immunopositive fibers in mesenteric arteries and veins. These results suggest that male mouse mesenteric vascular beds are useful for studying neural regulation of mesenteric arteries, which are innervated by adrenergic and CGRPergic nerves regulating vascular tone.

DOI： 10.1254/jphs.12014FP

The Mechanism of Calcitonin Gene-Related Peptide-Containing Nerve Innervation Reviewed

Narumi Hashikawa-Hobara, Naoya Hashikawa, Yoshito Zamami, Shingo Takatori, Hiromu Kawasaki

JOURNAL OF PHARMACOLOGICAL SCIENCES 119 ( 2 ) 117 - 121 2012.6

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE PHARMACOLOGICAL SOC

Calcitonin gene-related peptide (CGRP) is a major neurotransmitter and CGRP-containing primary sensory neurons play an important role in nociception and potent vasodilation. CGRP-containing nerves in mesenteric arteries are decreased in pathological animal models (hypertension, diabetes, and atherosclerosis). In apolipoprotein E knockout mice, which have atherosclerosis and peripheral sensory nerve defects, nerve growth factor (NGF)-mediated CGRP nerve facilitation was down-regulated, which may have been caused by the impairment of the Akt-NO-cGMP pathway. In addition, NGF-mediated CGRP neurite outgrowth was decreased in fructose-induced insulin-resistant rats. We recently discovered that renin angiotensin inhibitors improved CGR.P innervation in spontaneously hypertensive rats, indicating that rescuing CGRP nerve innervation might improve pathophysiological conditions. To find a novel reagent that facilitates CG.RP nerves, a new model, phenol-injured perivascular nerve model rats, was established. Adrenomedullin, hepatocyte growth factor, and angiotensin 11 type 2 receptor activation induced CGRP nerve distribution in phenol-injured rats. Furthermore, in insulin-resistant model rats, the down-regulation of CGRP nerves was likely due to the depression of phosphoinositide 3-kinase (PI3K)-dependent Akt activation. Administration of candesartan improves CGRPergic function via the PI3K Akt pathway in insulin-resistant rats. Thus, clarification of the mechanisms of CGRP nerve defects may constitute future therapeutic targets.

DOI： 10.1254/jphs.12R02CP

Involvement of perivascular nerves and transient receptor potential vanilloid 1 (TRPV1) in vascular responses to histamine in rat mesenteric resistance arteries Reviewed

Honghua Jin, Pengyuan Sun, Shingo Takatori, Toshihiro Koyama, Yoshito Zamami, Panot Tangsucharit, Yoshihisa Kitamura, Hiromu Kawasaki

EUROPEAN JOURNAL OF PHARMACOLOGY 680 ( 1-3 ) 73 - 80 2012.4

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

A previous report showed that histamine in denuded mesenteric vascular beds produced a triphasic response; an initial small histamine H-2 receptor-mediated vasodilation, a transient histamine H-1 receptor-mediated vasoconstriction, and finally a long-lasting vasodilation. We further investigated the vascular effect of histamine in mesenteric preparations without an endothelium to clarify the possible involvement of perivascular nerves. Male Wistar rat mesenteric vascular beds without an endothelium were perfused with Krebs solution containing methoxamine to produce active tone and lafutidine to block histamine H-2 receptor-mediated vasodilation. Histamine (1-100 mu M) was perfused for 1 min and perfusion pressure was measured with a pressure transducer. Histamine caused a biphasic vascular response; initial vasoconstriction followed vasodilation. Tetrodotoxin (a neurotoxin, 1 mu M) and procaine (a local anesthetic, 100 mu M) significantly inhibited the vasoconstriction and vasodilation. Ruthenium red (a transient receptor potential vanilloid 1 (TRPV1) antagonist, 1 mu M) also significantly inhibited both phases of the response. Pretreatment with capsaicin (a depletor of calcitonin gene-related peptide (CGRP)-containing nerves, 5 mu M) significantly inhibited the vasodilation without affecting the initial vasoconstriction. Both indomethacin (a cyclooxygenase inhibitor, 0.5 mu M) and seratrodast (a thromboxane A(2) receptor antagonist, 0.1 mu M) abolished the histamine-induced vasoconstriction and subsequent vasodilation. These results suggest that histamine-induced vasoconstriction and long-lasting vasodilation are mediated by activation of TRPV1 on capsaicin-sensitive and capsaicin-insensitive nerves. They also suggest that perivascular nerves and prostanoids, probably thromboxane A(2), are responsible for the vascular response to histamine. (C) 2012 Elsevier B. V. All rights reserved.

DOI： 10.1016/j.ejphar.2012.01.018

Candesartan Cilexetil Improves Angiotensin II Type 2 Receptor-Mediated Neurite Outgrowth via the PI3K-Akt Pathway in Fructose-Induced Insulin-Resistant Rats Reviewed

Narumi Hashikawa-Hobara, Naoya Hashikawa, Yusuke Inoue, Hitomi Sanda, Yoshito Zamami, Shingo Takatori, Hiromu Kawasaki

DIABETES 61 ( 4 ) 925 - 932 2012.4

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER DIABETES ASSOC

We have shown previously that stimulation of the angiotensin type 2 receptor (AT(2)R) results in nerve facilitation. In this study, we determined the capacity of candesartan to correct expression patterns characteristic of neuropathy and AT(2)R-mediated neurite outgrowth in the fructose-induced insulin-resistant rat, which is one of the human hyperinsulinemia models. Wistar rats received a 15% (w/v) fructose solution in their drinking water for 4 weeks (fructose-drinking rats [FDRs]), with or without candesartan (5 mg/kg/day). We evaluated physiological and behavioral parameters and performed immunohistochemical studies. We found that the FDR developed insulin resistance and downregulated both AT(2)R neuronal function and phosphorylated Akt expression in dorsal root ganglia (DRG) neurons. Candesartan improved neurite outgrowth in the FDR, which was associated with the restoration of AT(2)R and phosphorylated Akt expression. Furthermore, downregulation of phosphoinositide 3-kinase (PI3K) inhibited AT(2)R-mediated neurite outgrowth in control DRG cells. PI3K activation increased AT(2)R-mediated neurite outgrowth and phosphorylated Akt expression in FDR DRG cells. These results suggest that the decrease of AT(2)R-mediated neurite outgrowth in FDRs is likely to be the result of decreased PI3K-dependent Akt activation. Candesartan improved AT(2)R neuronal function and Akt phosphorylation, which were associated with sensory nerve defects and insulin sensitivity in the FDR. Diabetes 61:925 932, 2012

DOI： 10.2337/db11-1468

Anandamide Induces Endothelium-Dependent Vasoconstriction and CGRPergic Nerve-Mediated Vasodilatation in the Rat Mesenteric Vascular Bed Reviewed

Chihiro Tamaki, Hideki Nawa, Shingo Takatori, Sakiko Oda, Toshiaki Sendo, Yoshito Zamami, Hiromu Kawasaki

JOURNAL OF PHARMACOLOGICAL SCIENCES 118 ( 4 ) 496 - 505 2012.4

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE PHARMACOLOGICAL SOC

An endogenous cannabinoid anandamide (N-arachidonoylethanolamide) has been shown to cause vasodilatation in vitro and a brief vasoconstriction followed by prolonged depressor response in vivo. This study investigated the vascular effects of anandamide and underlying mechanisms in rat mesenteric vascular beds. In preparations with an intact endothelium and active tone, anandamide at low concentrations (0.1 - 1 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation, but at high concentrations (10 nM - 1 mu M) elicited an initial and sharp increase in perfusion pressure due to vasoconstriction followed by long-lasting vasodilatation in a concentration-dependent manner. Treatment with SR141716A [cannabinoid-1 (CB1)-receptor antagonist] blunted both the vasoconstrictor and vasodilator responses. Also, removal of the endothelium and indomethacin (cyclooxygenase inhibitor), but not adrenergic denervation with 6-hydoxydopamine (adrenergic neurotoxin), markedly inhibited the vasoconstrictor response to anandamide, while these treatments did not affect vasodilatation. The vasodilatation, but not vasoconstriction, in response to anandamide was markedly attenuated by capsazepine [selective antagonist for transient receptor potential vanilloid-1 (TRPV1)], pretreatment with capsaicin [calcitonin gene related peptide (CGRP)ergic-nerve depletor], or cold-storage denervation. These results suggest that in rat mesenteric vascular beds, anandamide causes CB1-receptor and prostanoid-mediated endothelium-dependent vasoconstriction and perivascular capsaicin-sensitive CGRPergic nerve-mediated vasodilatation.

DOI： 10.1254/jphs.11236FP

Adrenergic Stimulation-Released Histamine Taken-up in Adrenergic Nerves Induces Endothelium-Dependent Vasodilation in Rat Mesenteric Resistance Arteries Reviewed

Yuto Haruki, Shingo Takatori, Sayo Hattori, Yoshito Zamami, Toshihiro Koyama, Panot Tangsucharit, Hiromu Kawasaki

JOURNAL OF PHARMACOLOGICAL SCIENCES 118 ( 4 ) 537 - 542 2012.4

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE PHARMACOLOGICAL SOC

The present study investigated whether histamine was taken up by perivascular adrenergic nerves and released by periarterial nerve stimulation (PNS) to induce vascular responses. In rat mesenteric vascular beds treated with capsaicin to eliminate calcitonin gene related peptide (CGRP)ergic vasodilation and with active tone, PNS (1 - 4 Hz) induced only adrenergic nerve-mediated vasoconstriction. Histamine treatment for 20 min induced PNS-induced vasoconstriction followed by vasodilation without affecting CGRP-induced vasodilation. Chlorpheniramine, guanethidine, combination of histamine and desipramine, and endothelium-removal abolished PNS-induced vasodilation in histamine-treated preparations. These results suggest that histamine taken up by and released from adrenergic nerves by PNS causes endothelium-dependent vasodilation in rat mesenteric arteries.

DOI： 10.1254/jphs.12012SC

Quinolone analogs 11: Synthesis of novel 4-quinolone-3-carbohydrazide derivatives with antimalarial activity Reviewed

Yoshihisa Kurasawa, Kiminari Yoshida, Naoki Yamazaki, Eisuke Kaji, Kenji Sasaki, Yoshito Zamami, Yasuhiro Sakai, Takatoshi Fujii, Hideyuki Ito

JOURNAL OF HETEROCYCLIC CHEMISTRY 49 ( 2 ) 288 - 292 2012.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

The reaction of the 6-substituted 1-methyl-4-quinolone-3-carboxylates 10a,b with hydrazine hydrate gave the 3-carbohydrazides 7a,b, respectively, whose reaction with 2-, 3-, and 4-pyridinecarbaldehydes afforded the 3-(N2-pyridylmethylene)carbohydrazides 8ac and 9ac. The Curtius rearrangement of compound 7b provided the N,N'-bis(4-quinolon-3-yl)urea 14 presumably via the 3-carboazide 11 and then 3-isocyanate 12. Compounds 7a, 8a, and 9a were found to possess antimalarial activity from the in vitro screening data. J. Heterocyclic Chem.,(2011).

DOI： 10.1002/jhet.774

Endothelium-Derived Relaxing Factor Mediated Vasodilation in Mouse Mesenteric Vascular Beds Reviewed

Hiroki Fujiwara, Yoshihiro Wake, Narumi Hashikawa-Hobara, Kento Makino, Shingo Takatori, Yoshito Zamami, Yoshihisa Kitamura, Hiromu Kawasaki

JOURNAL OF PHARMACOLOGICAL SCIENCES 118 ( 3 ) 373 - 381 2012.3

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE PHARMACOLOGICAL SOC

The endothelium in rat mesenteric vascular beds has been demonstrated to regulate vascular tone by releasing mainly endothelium-derived hyperpolarizing factor (EDHF), which is involved in the activation of K+ channels and gap-junctions. However, it is unclear whether the endothelial system in mouse resistance arteries contributes to regulation of the vascular tone. The present study was designed to investigate the role of the endothelium using acetylcholine and A23187 (Ca2+ ionophore) in mesenteric vascular beds isolated from male C57BL/6 mice and perfused with Krebs solution to measure perfusion pressure. In preparations with active tone produced by methoxamine in the presence of guanethidine, injections of acetylcholine, A23187, and sodium nitroprusside (SNP) caused a concentration-dependent decrease in perfusion pressure due to vasodilation. The vasodilator responses to acetylcholine and A23187, but not SNP, were abolished by endothelium dysfunction and significantly inhibited by N-omega-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) and tetraethylammonium (K+-channel inhibitor) but not glibenclamide (ATP-sensitive K+-channel inhibitor). Indomethacin (cyclooxygenase inhibitor) significantly blunted only A23187-induced vasodilation, while 18 alpha-glycyrrhetinic acid (gap-junction inhibitor) attenuated only acetylcholine-induced vasodilation. These results suggest that the endothelium in mouse mesenteric arteries regulates vascular tone by prostanoids, EDHF, and partially by nitric oxide, different from the endothelium of rat mesenteric arteries.

DOI： 10.1254/jphs.11197FP