Faculty Profiles - ZAMAMI Yoshito

MISC - ZAMAMI Yoshito

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ラット腸間膜動脈におけるヒスタミン誘発血管弛緩反応に及ぼす塩酸レボカバスチンおよび塩酸オロパタジンの影響

KOYAMA TOSHIHIRO, NARAHARA YUKIMI, SON HOEN, RI SHIBIN, KIN SHIN, ZAMAMI YOSHITO, TAKATORI SHINGO, KITAMURA YOSHIHISA, KAWASAKI HIROMU

アレルギー・免疫 17 ( 4 ) 662 - 670 2010.3

簡易懸濁用容器「けんだくん」を用いた光に不安定な薬剤の含量減少の抑制について

座間味義人, 東恩納司, 安藤哲信, 武藤浩司, 天野学, 倉田なおみ, 合葉哲也, 北村佳久, 松永尚, 千堂年昭, 黒崎勇二, 佐々木健二, 川崎博己, 五味田裕

日本薬学会年会要旨集 130th ( 4 ) 284 - 284 2010.3

Role of Angiontensin Receptors on Remodeling Perivascular Nerves

HOBARA Narumi, GODA Mitsuhiro, HASHIKAWA Naoya, JIN Xin, ZAMAMI Yoshito, TAKATORI Shingo, KAWASAKI Hiromu

YAKUGAKU ZASSHI 130 ( 11 ) 1421 - 1425 2010

Language：Japanese Publisher：The Pharmaceutical Society of Japan

The aim of this study was to investigate age-related changes in the density of calcitonin gene-related peptide (CGRP)-containing nerve fibers in spontaneously hypertensive rats (SHR) and the effects of long-term inhibition of the renin-angiotensin system on these changes. An age-related decrease in the density of CGRP-like immunoreactive (LI)-containing nerve fibers but not neuropeptide Y (NPY)-LI-containing sympathetic nerve fibers was found in the mesenteric artery of SHR but not Wistar-Kyoto rats (WKY). The density of NPY-LI-containing nerve fibers was significantly greater in SHR than in WKY. SHR were treated for 7 weeks with angiotensin-converting enzyme inhibitor (0.005% temocapril), angiotensin II type-1 (AT1) receptor antagonist (0.025% losartan), or vasodilator (0.01% hydralazine) in their drinking water. Each drug treatment significantly lowered the systolic blood pressure measured using the tail-cuff method. Long-term treatment of SHR with temocapril and losartan significantly increased the density of CGRP-LI-containing nerve fibers in mesenteric arteries. Furthermore, to clarify the effect of the angiontensin II type-2 (AT2) receptor in the restoration of perivascular nerve innervation, we used the phenol-injured rat model, in which the perivascular nerves are markedly reduced by the topical application of phenol. Activation of AT2R significantly restored CGRP-LI innervation in phenol-injured rats. These results suggest that selective stimulation of AT2 receptors facilitates reinnervation of mesenteric perivascular CGRP-containing nerves.

DOI： 10.1248/yakushi.130.1421

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Effects of calcitonin gene-related peptide-containing (CGRPergic) nerve depletion on perivascular nerve function in fructose-drinking rats (FDR)

Miho Hosoda, Kumiko Iwata, Yoshito Zamami, Hiromu Kawasaki

JOURNAL OF PHARMACOLOGICAL SCIENCES 112 243P - 243P 2010

Characterization and age-related changes in endothelial modulation of vasoconstriction in resistance artery

Xin Jin, Yukiko Otonashi, Yoshito Zamami, Narumi Hobara, Toshihiro Koyama, Pengyuan Sun, Simin Li, Yoshihisa Kitamura, Hiromu Kawasaki

JOURNAL OF PHARMACOLOGICAL SCIENCES 112 18P - 18P 2010

簡易懸濁法導入・活用事例から探るアイディア&ヒント医薬品情報 2 安定性・配合変化(2) 光に不安定な薬は簡易懸濁法で投与できる?

ZAMAMI YOSHITO, ANDO TETSUAKI

薬局 60 ( 8 ) 2925 - 2928 2009.7

Proton as a Possible Neurotransmitter for Perivascular Axo-axonal Transmission in the Rat Mesenteric Resistance Artery

Hiromu Kawasaki, Satoko Miyashita, Yoshito Zamami, Toshihiro Koyama, Mitsunobu Goda, Xin Jin, Yukiko Iwatani

Tzu Chi Medical Journal 21 ( 2 ) 95 - 98 2009.6

Language：English Publishing type：Book review, literature introduction, etc.

The rat mesenteric resistance arteries are densely innervated by adrenergic vasoconstrictor nerves, CGRPergic vasodilator nerves and nitric oxide-containing nerves. Those nerves have axo-axonal interactions to modulate vascular nerve function and to regulate vascular tone. The present study focused on a possible transmitter, which is involved in axo-axonal transmission of adrenergic nerves and CGRP nerves. When nicotine is applied in the rat perfused mesenteric artery, nicotine stimulates nicotinic α3β4 nicotinic acetylcholine receptors on adrenergic nerves. This stimulation leads to the release of proton from adrenergic nerves. Released proton activates transient receptor potential vanilloid-1 receptors on neighboring CGRP nerves and CGRP is released to cause vasodilation. The present findings would explain why CGRPergic nerves, which are capsaicin-sensitive sensory nerves, have efferent function in spite of being primary afferent nerves. Namely, efferent adrenergic nerves, which momentarily and constantly regulate the vascular tone, may send their information to the neighboring CGRPergic nerves. Proton may be used as the transmitter for axo-axonal transmission to counteract excess vasoconstriction as the efferent function of afferent sensory nerves. Recent study demonstrated that periarterial nerve stimulation of perfused mesenteric arteries resulted in a decrease in the pH level of the perfusate concomitant with CGRPergic nerve-mediated vasodilation, which was abolished by the adrenergic neuron blocker, guanethidine. These findings suggest that proton acts as a transmitter for axo-axonal transmission between adrenergic and CGRPergic nerves in mesenteric resistance arteries. In conclusion, the present study presents evidence that perivascular nerves have strong axo-axonal interaction to modulate nerve function and to regulate vascular tone. © 2009 Buddhist Compassion Relief Tzu Chi Foundation.

DOI： 10.1016/S1016-3190(09)60018-5

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腸間膜動脈抵抗血管の内皮細胞による血管緊張調節の特性

金シン, 音無由紀子, 座間味義人, 小山敏広, 孫鵬遠, 川村直美, 坪井崇, 山口康代, 上田太郎, 北村佳久, 川崎博己

日本薬学会年会要旨集 129th ( 1 ) 260 2009.3

Functional Alteration of Nervous System in Renovascular Hypertension(Symposium Review)

KOYAMA Toshihiro, HATANAKA Yukako, GODA Mitsuhiro, ZAMAMI Yoshito, HOBARA Narumi, KAWASAKI Hiromu

Journal of the Pharmaceutical Society of Japan 129 ( 2 ) 185 - 189 2009.2

Language：Japanese Publisher：The Pharmaceutical Society of Japan

The role of nitric oxide (NO)-containing nerves in adrenergic neurotransmission in hypertension was studied in mesenteric resistance arteries without endothelium in 2-kidney-1-clip renal hypertensive rats (2K-1C RHR) and shamoperated normotensive rats (Sham-R). Mesenteric vascular beds isolated from 2K-1C RHR and Sham-R were perfused with Krebs solution and changes in perfusion pressure were measured with a pressure transducer. Perfusion of a NO synthase inhibitor, N-ω-nitro-L-arginine methyl ester (L-NAME), markedly augmented vasoconstrictor responses to periarterial nerve stimulation (PNS) without affecting vasoconstriction induced by exogenously injected noradrenaline. L-NAME significantly increased the neurogenic release of NA evoked by PNS in both 2K-1C RHR and Sham-R preparations. The facilitatory effect of L-NAME based on the inhibition of NO production in 2K-1C RHR was less than that in Sham-R. These results suggest that the function of NO-containing nerves, which presynaptically inhibit adrenergic neurotransmission, is decreased in the renovascular hypertensive, model rat.

DOI： 10.1248/yakushi.129.185

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2‐Kidney,1‐Clip(2K‐1C)高血圧ラット腸間膜動脈の血管周囲交感神経亢進におけるAngiotensin受容体の関与

小山敏広, 畑中由香子, 芳原成美, 合田光寛, 座間味義人, 北村佳久, 川崎博已

血管 32 ( 1 ) 22 2009.1

Cardiovascular responses and drug evaluation using the pithed rate model

ZAMAMI Yoshito, TAKATORI Shingo, KAWASAKI Hiromu

Folia Pharmacologica Japonica 133 ( 1 ) 22 - 26 2009.1

Language：Japanese Publisher：The Japanese Pharmacological Society

脊髄穿刺モデルは，循環反射の関与を除外した状態で各種血管作動性物質による心血管反応をin vivo系で観察することができるだけでなく，穿刺ロッドを介した電気刺激により各種神経性の心血管反応とこれに対する薬効評価も観察できるため，末梢における心血管反応の評価に有用である．モデル作製では，ラットを用い，ペントバルビタール麻酔下に眼窩より脊柱内にロッドを挿入し，仙髄までの脊髄を破壊し，人工呼吸下に，頚動脈に挿入したカニューレを介して全身血圧および心拍数を測定記録した．血圧および心拍数が安定した後，穿刺ロッドを介して胸髄上部を電気刺激すると心拍数の増加を伴った刺激頻度依存性の血圧上昇反応，胸髄下部刺激では心拍数の増加を伴わない刺激頻度依存性の血圧上昇反応が観察される．この昇圧反応は，遠心性交感神経による血管収縮反応である．メトキサミンで平均血圧を人工的に約100 mmHgに上昇維持し，ヘキサメソニウムで自律神経を遮断した条件で，電気刺激を行うと，心拍数の増加を伴わない刺激頻度依存性の血圧下降反応が観察される．この降圧反応は，CGRP作動性神経による血管拡張反応である．脊髄穿刺SHRでは，CGRP神経性血管反応の減弱が観察されるが，これがSHRの交感神経性血管反応の増大を招き，高血圧の進展・維持に関与している可能性を示唆する．脊髄穿刺インスリン抵抗性ラットでは慢性的な高インスリン血症状態が交感神経性血管反応の増大とCGRP神経性血管反応の減弱が生じていることから，これら神経の機能的な変化が高血圧症状を誘導すると考えられる．一方，脊髄穿刺ラットの実験で，nNOS神経が交感神経からのノルアドレナリン遊離を抑制することで，過度の血管収縮を抑制し血管の緊張度を調節していることも示唆できる．これらの研究から，脊髄穿刺モデルはin vivo系における神経性心血管反応とこの反応に対する薬効評価ができる有用なモデルであると考えられる．<br>

DOI： 10.1254/fpj.133.22

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Cardiovascular responses and drug evaluation using the pithed rate model

ZAMAMI Yoshito, TAKATORI Shingo, KAWASAKI Hiromu

Folia Pharmacologica Japonica 133 ( 1 ) 22 - 26 2009.1

Language：Japanese Publisher：The Japanese Pharmacological Society

DOI： 10.1254/fpj.133.22

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