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The Blocking Effects of Tolazoline and Propranolol on Axial Movements of Incisor Teeth and on Changes in Arterial Blood Pressure Induced by Adrenaline in Rats

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The Blocking Effects of Tolazoline and Propranolol on Axial Movements of Incisor Teeth and on Changes in Arterial Blood Pressure Induced by Adrenaline in Rats Jpn. J. Oral Biol.,40: 497-505, 1998. ORIGINAL The blocking effects of tolazoline and propranolol on axial movements of incisor teeth and on changes in arterial blood pressure induced by adrenaline in rats Hiroko Yamazaki and Shizuyo Yamaguchi Department of Pharmacology, School of Dental Medicine, Tsurumi University 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan 〔Received on June 26, 1998; Accepted on August 3, 1998〕 Key words: adrenaline/adrenergic blocker/tooth movement/rat incisor/blood pressure Abstract: Axial tooth movements and arterial blood pressure were measured following intravenous injec- tion of adrenaline,1hr before, and 1 and 2hr after the injection of tolazoline (an α-adrenergic blocking agent) or propranolol (a β-adrenergic blocking agent). The initial increase in blood pressure induced by adrenaline was significantly suppressed and the successive decrease in blood pressure was markedly enhanced by pretreatment with tolazoline. In contrast to blood pressure changes, the initial extrusive tooth movement induced by adrenaline was not suppressed, and successive intrusive tooth movements induced by adrenaline were not potentiated, but suppressed. The initial increase in blood pressure induced by adrenaline was enhanced and the successive decrease in blood pressure was suppressed by pretreatment with pro- pranolol. On the other hand, the initial extrusive tooth movement induced by adrenaline was not significantly potentiated, but successive intnsive tooth movements induced by adrenaline were markedly suppressed. Pressure within the socket that may induce axial tooth movements might be regulated by various factors, such as resistance of the blood vessels, blood flow in the socket, and systemic arterial blood pressure, all of which are liable to change following an injection of adrenaline under the influence of α-or β-adrenergic blockers. 抄 録:本 研 究 に お い て は ア ドレ ナ リ ン投 与 に よ る ラ ッ ト全身 血 圧 の変 動 と下 顎 切 歯 の 動 き に対 す る トラ ゾ リ ン (α 遮 断 薬)と プ ロ プ ラ ノ ロー ル(β 遮 断 薬)前 投 与 の 影 響 を調 べ た 。 トラ ゾ リ ン前 投 与 に よ り,ア ドレ ナ リ ン に よ る 初 期 の 血 圧 上 昇 は有 意 に抑 制 さ れ,そ れ に続 く血 圧 下 降 は著 明 に促 進 さ れ た 。 一 方,ア ド レ ナ リ ン に よ る 初 期 の 歯 の 突 出 運 動 は 抑 制 され ず,そ れ に続 く歯 の 引 込 み 運 動 は促 進 さ れ な か っ た 。 プ ロ プ ラ ノ ロ ー ル 前 投 与 に よ り血 圧 上 昇 は促 進 され,血 圧 下 降 は ほ ぼ 完 全 に 抑 制 され た 。 一 方,歯 の 突 出運 動 は 促 進 さ れ ず,引 込 み 運 動 は 著 明 に 抑 制 され た 。以 上 の 結 果 か ら,ア ド レナ リ ン に よ る 全 身 血 圧 の上 昇 は α 遮 断 薬 に よ り抑 制 さ れ β 遮 断 薬 に よ り促 進 さ れ る こ と,血 圧 下 降 は α 遮 断 薬 に よ り促 進 され β 遮 断 薬 に よ り抑 制 さ れ る こ とが 判 明 した 。一 方,歯 の 突 出運 動 お よ び 引 込 み 運 動 は,全 身 血 圧 変 動 と必 ず し も一 致 しな い こ とが 判 明 し た 。 歯 の 動 き を 引 き起 こす と考 え ら れ る顎 骨 内 の 圧 力 変 化 は,全 身 血 圧 の み な らず,血 管 抵 抗 性,血 流 量 な ど さ ま ざ まな 要 因 に よ り調 節 さ れ て いる可能性が示唆された。 498 Jpn. J. Oral Biol.,40: 497-505,1998. movement and adrenergic receptors. Introduction Materials and Methods Adrenaline induces a dose-dependent rapid extrusivemovement of the rat incisoralmost simulta- 1. Animals neously with an increasein systemic arterialblood Male Wistar rats (n=20), weighing 321 to 357g at pressure,followed by intrusivetooth movement and a 10 to 13 weeks of age, were divided into two equal decrease in blood pressure1).We previouslysuggested groups. They were immobilized by the method de- that extrusivetooth movement is primarilyrelated to scribedpreviously9). In brief,the rats were placed in a the risein arterialblood pressuredue to stimulationof supine positionand anesthetizedvia inhalationof 1.1 vascular α-adrenergic receptors and that stimulation % halothane in air through a trachealtube connected of β-adrenergic receptors in the localized vasculature to an artificialrespirator at 100 strokes/min (3ml/ within the incisor socket causes a reduction in pres- stroke). The lower margin of the jaw bone was surgi- sure and blood volume, followed by marked intrusive cally exposed and secured with a hemostat, which was tooth movement1). affixed to the metal bar of a magnetic stand with Aars2) and Aars and Linden3) reported that sympa- acrylic resin. Each rat was administered atropine thetic nerve stimulation induces intrusive tooth move- sulfate (25μg) before the operation to prevent tra- ment by altering blood pressure and volume in the cheal secretion. Rectal temperature was maintained periodontal ligament of the rabbit incisor and cat at 35℃ using a heating pad during the experimental canine. They suggested that these responses are period. A polyethylene tube was inserted into the left mediated by α-adrenergic receptors because intrusive hind leg vein; through which, drugs were administer- tooth movement is greatly reduced by injection of the ed to each rat at 1-hr intervals. α-adrenergic blocking agent, phentolamine. Adminis- tration of noradrenaline, a potent stimulator of α- 2. Administration of drugs adrenergic receptors4), also induces intrusive tooth Two experiments were performed as follows. movements in the rabbit incisor5,6) and in the cat Experiment 1. In one group of 10 rats, each animal canine7). was given an intravenous injection of 1mg/kg body In addition, β-adrenergic antagonists induce a wt of tolazoline, a known α1-and α2-adrenergic recep- marked extrusion of the tooth8). Aars8) suggested that tor blocker (Imidaline, Yamanouchi Seiyaku Co., a reduction in β-adrenergic tone leads to a rise in Tokyo). One hour before (control), and 1 and 2hr pressure and volume in the vessels within the per- after the injection of tolazoline, each animal was iodontal ligament and, therefore, to extrusion of the given intravenous injections of adrenaline (1μg/kg) rabbit incisor. Furthermore, subsequent injection of (Daiichi Seiyaku Co., Tokyo). isoprenaline, a potent stimulator of β-adrenergic recep- Experiment 2. In the other group of 10 rats, each tors, always induces rapid intrusions of the teeth. animal was given an intravenous injection of pro- Nevertheless, the precise relationship between pranolol (2mg/kg), a known β1-and β2-adrenergic extrusive or intrusive tooth movements and stimula- receptor blocker (Sigma, St. Louis , MO, U.S.A.). As tion or inhibition of vascular α-and β-adrenergic in Experiment 1, 1hr before (control) , and 1 and 2hr receptors in continuously erupting incisors remains after the injection of propranolol, each animal was unclear. given intravenous injections of adrenaline (1μg/kg). The purposes of the present study were to investi- In both Experiments 1 and 2, the drugs were dissolved gate the effects of adrenaline on axial movements of in physiological saline. The volume of injected solu- the rat mandibular incisor and arterial blood pressure tions was 0.1ml/100g body weight. in rats pretreated with α-or β-adrenergic blocking drugs, and to elucidate the relationship between tooth H. Yamazaki, et al.: Adrenergic blockers and tooth movement 499 3. Axial movements of the incisor intervals during the experimental period. Axial movement of the leftmandibular incisorwas measured by a non-contacting displacement detec- 5. Maximum tooth movement and blood pressure tor; that is, the movement of a thin metal plate change attachedto the toothsurface was recorded9).Data was Tooth positions at the maximum extrusive move- fed into a computer (PC-9801DA; NEC, Tokyo) at ment (peak point), maximum intrusive movement 1-sec intervals.The values recorded by the detector (bottom point), and recovery (recovery point), and were correctedfor the curvatureof the incisorand the arterial blood pressures at the maximum increase radial distance between the tooth surface and the (peak point),maximum decrease (bottom point),and metal plate9). recovery (recovery point) were examined following injectionsof adrenaline before and after an injection 4. Arterial blood pressure of tolazoline or propranolol. Arterialblood pressure was measuredusing a pres- suretransducer (MP-15, Micron Instruments,CA, U. 6. Statisticalanalysis S.A.); thatis, a polyethylenetube was insertedinto Differencesof the mean values were compared by the mid-tailartery; and throughwhich ,the pressure Scheffe'smethod for multiplecomparisons afteranal- was recorded.The arterialblood pressurewas fed ysisof variance (ANOVA). intoa computer (PC-9801DA; NEC, Tokyo) at 1-sec Fig. 1 Records of tooth displacement (upper column) and arterial blood pres- sure (lower column) following the injection of adrenaline, 1hr before (control), and 1 and 2hr after the injection of tolazoline (α-adrenergic blocking agent). Points (arrow heads) a, b, and c indicate peak, bottom, and recovery of the tooth displacement, respectively; points a',b', and c', indicate peak, bottom, and recovery of the arterial blood pressure, respectively. Arrows indicate the time of drug injection (designated as 0 min). Each curve was obtained from combined values for ten animals . 500 Jpn. J. Oral Biol., 40: 497-505, 1998. suppressive effect of tolazoline.After the injectionof Results tolazoline,the initialincrease in arterial blood pres- sure by adrenaline was markedly suppressed, but a 1.
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