The bradycardiac and presor to intravenous and intraventricular methoxamine were examined in urethane-anesthetized rabbits 1) Intravenous methoxamine produced bradycardiac pressor responses. Atropine (2 mg/kg, i,v.) weakened but not abloished the bradycardiac effect. 2) The bradycardiac effect elicited by intravenous methoxamine was not affected by int-ravenous prazosin, rehimbiine, guanethidine and propranolol, butt was attenuated by intra venous chlorisondamine reserpine. 3) The pressor effect elioited by intravenous methoxamine was weakened by prazosin, but was scarcely affected, rather potentiated, by intraTenous yohimblne, guanethidine, chlorisondamine, propranolol and resperpine. 4) Intraventricular methoxamine produced pressor and bradycardiac responses. 5) The bradycardiac effect elicited by intraventricular methoxamine was net affected by intravenous atropine, prasosin and yohimbine. This was attenuated by intravenous guane- thidine, chlorisondamine, propranolol and reserpine, and by intraventricular atropine prazosin and propranolol, respectively. 6) The pressor effect elicited by intraventricular methoxamine was attenuated by intra- ventricular and intravenous prazosin. This was not affected by intravenous atropine, gua-nethidine, chlorisondamine, propranolol, reserpine and yohimbine, and by intraventricular atropine, prasosin and Propranolol, respectivelr. 7) From these results it was inferred that bradycardiac effect elicited by methoxamine was not an action through the mediation of aleph 1-adrenoceptors but was a result from non-specific actions on some brain receptors.
Atropine ; Brain ; Chlorisondamine ; Guanethidine ; Methoxamine* ; Negotiating ; Prazosin ; Propranolol ; Rabbits* ; Reserpine ; Yohimbine

No abstract available.
Bupivacaine* ; Clonidine* ; Yohimbine

BACKGROUND: Ischemic preconditioning(IP) is known to be effective in the protection of myocardial necrosis, arrhythmia, and the restoration of the myocardial function in the ischemia-reperfusion state of the heart. However the exact mechanism is not clearly understood. The purpose of this study was to elucidate the trigger mechanism of IP on the restoration of the myocardial function after ischemia-reperfusion. MATERIAL AND METHOD: By connecting a Langendorff perfusion apparatus with an isolated heart of a rat, the normal temperature of the heart was maintained. The experiment was conducted in seven groups, which were divided according to the preconditioning stimuli and blockage methods: Group I(n=10) was a group without IP, Group II(n=10) a group of three-minute IP, Group III(n=10) a group of PEIP, Group IV(n=10) a group of clonidine IP, Group V(n=10) a group of IP after reserpine, Group VI(n=10) a group of PE & prazosin IP, and Group VII(n=10) a group of clonidine & yohimbine IP. Hemodynamic parameters of DP, LVEDP, +/-dP/dT and the changes of perfusion in the coronary artery were evaluated. RESULT: Developed pressure and +dP/dT changed per unit time. After 20 minutes of reperfusion, those of Group II and III were 63.1+/-3.7%, 64.8+/-4.6% and 64.5+/-4.6%, 63.8+/-4.4%, which improved more significantly than those of Group I(P<0.05). However, there were no significant differences between the Groups V and VI, and Group I. CONCLUSION: The Brief ischemic preconditioning and pharmacological preconditioning using alpha-receptor sympathomimetics have protecting effects on the restoration of myocardial function after reperfusion. And the protecting effect of preconditioning seems to be related to sympathetic neurotransmitters and to the selective action of the alpha1-adrenergic receptor.
Animals ; Arrhythmias, Cardiac ; Clonidine ; Coronary Vessels ; Heart ; Hemodynamics ; Ischemic Preconditioning ; Ischemic Preconditioning, Myocardial* ; Necrosis ; Neurotransmitter Agents ; Perfusion ; Prazosin ; Rats* ; Reperfusion ; Reserpine ; Sympathomimetics ; Yohimbine

1) The author investigated whether presynaptic alpha-adrenoceptors exist in the cardioaccelerator nerves of cold-blooded animals(frog, tortoise) as in ones of in mammals. 2) Each atrial preparation of a frog, tortoise and guinea-pig produced the positive chronotropic and inotropic responces to field stimulation. Each ventricular muscle preparation of frog and tortoise produced positive inotropic responces to field stimulation. 3) Both the responces of frog atrium and the inotropic response of frog ventrice to the stimulation were abolished or markedly inhibited by the presence of tetrodotoxin, guanethidine and proparanolo. Both responses of tortoise atrium to the stimulation were markedly inhibited by propranolol and the inotropic response ventricle to the stimulation was markedly inhibited by tetrodotoxin. 4) Both responses of frog and tortoise atrium, and the inotropic response of frog and tortoise ventricle to the stimulation were not affected by clonidine and yohimbine. 5) Both responses of guinea-pig atrium to the stimulation were markedly inhibited in the presence of clonidine and this clonidine-induced inhibition was not observed in the presence of yohimbine. 6) The above results suggest that presynaptic alpha-adrenoceptors do not exist in the cardioaccelerator nerves of frog and tortoise, being different from those of mammalisn animals.
Animals* ; Clonidine ; Guanethidine ; Mammals ; Propranolol ; Tetrodotoxin ; Yohimbine

The effects of intraventricular alpha2-adrenoceptor agonist and antagonist, clonidine and rauwolscine, on changes of blood pressure induced by the rise of intracranial pressure were investigated in urethane-anesthetized rabbits. 2) The rise of ICP, induced by the infusion of saline into a balloon placed in the epidural space, was comparatively slow in the beginning of the infusion but became sharp as the infusion proceeded. Corresponding with the gradual increase of ICP, there was a slight decrease in BP. An abrupt rise of BP was observed when ICP showed a sharp increase. 3) Intraventricular rauwolscine 5(microgram) by itself did not affect BP. In these rauwolscine-treated rabbits the increase of both ICP and BP by the infusion was similar to that of the control animals. 4) The pretreatment with rauwolscine 50(microgram) did hardly affect BP, but this made the increase of ICP and BP by the infusion different from that of the control animals. The slight hypotensive response in the beginning of the infusion did not appear and the pressor response to the raised ICP was markedly facilitated. The volume of saline inused into the infusing balloon to cause the same increase of ICP as in the control animals was much smaller than in the control ones, and the magnitude of the maximal increase of BP was much greater. 5) The pretreatment with 500 microgram of intraventricular rauwolscine produced an increase of BP. In these animals the increase of both ICP and BP by the infusion seemed to be slightly facilitated than in the control animals. 6) Intraventricular clonidine 30(microgram) markedly decreased BP. In these clonidine-treated animals the slight hypotensive response in the beginning was more distinct than in the control animals, and the pressor response was hardly seen. 7) The hypotensive response to intraventricular clonidine 30(microgram) was weakened in the animals pretreated with intraventricular rauwolscine 500(microgram). In these animals the increase of both ICP and BP by the infusion appeared as in the control animals. 8) The above results suggest that the pressor response to the raised ICP in rabbits was inhibited under the condition of stimulation of central alpha2-adrenoceptors and facilitated under the condition of blockade of the receptors. It seems that the rise of blood pressure takes place when the activity of alpha2-adrenoceptors is impared by the increased pressure of the balloon placed in the epidural space.
Animals ; Blood Pressure ; Clonidine ; Epidural Space ; Intracranial Pressure* ; Rabbits* ; Yohimbine

Although quantitative EEG parameters, such as spectral band powers, are sensitive to centrally acting drugs in dose- and time-related manners, changes of the EEG parameters are redundant. It is desirable to reduce multiple EEG parameters to a few components that can be manageable in a real space as well as be considered as parameters representing drug effects. We calculated factor loadings from normalized values of eight relative band powers (powers of 0.5, 1.0~2.0, 2.5~4.0, 4.5~5.5, 6.0~8.0, 8.5~12.0, 12.5~24.5, and 25~49.5 Hz bands expressed as ratios of the power of 0.5-49.5 Hz band) of EEG during pre-drug periods (11:00~12:00) by factor analysis and constructed a two-dimensional canonical space (reference canonical space) by canonical correlation analysis. Eight relative band powers of EEG produced by either physostigmine or yohimbine were reduced to two canonical scores in the reference canonical space. While changes of the band powers produced by physostigmine and yohimbine were too redundant to describe the difference between two drugs, locations of two drugs in the reference canonical space represented the difference between two drug's effects on EEG. Because the distance between two locations in the canonical space (Mahalanobis distance) indicates the magnitude of difference between two different sets of EEG parameters statistically, the canonical scores and the distance may be used to quantitatively and qualitatively describe the dose-dependent and time-dependent effects and also tell similarity and dissimilarity among effects. Then, the combination of power spectral analysis and statistical analysis may help to classify actions of centrally acting drugs.
Animals ; Electroencephalography ; Factor Analysis, Statistical ; Physostigmine ; Rats ; Yohimbine

1) The effects of various alpha-adrenoceptor antagonists on the pressor responses to norepinephrine and phenylephrine were examined in anesthetized rabbits in an attempt to determine whether alpha1 and alpha2-adrenoceptors are located on vascular smooth muscle. 2) yohimbine and piperoxan caused a much greater reduction in the pressor responses(rise of 30~50mmHg) to norepinephrine than to phenylephrine, where as labetalol, thymoxamine, phentolamine and prazosin showed a much greater selectively in reducing the pressor responses to phnylephrine than to norepinephrine. 3) The prssor action of small dose of norepinephrine(rise of 10~20mmHg) was not significantly inhibited by the doses of labetalol, thymoxamine and prazosin which caused marked reduction of the above phenylephrine pressor responses, but yohimbine, piperoxan and phentolamine weakend the action significantly. 4) The results suggest that there are two types, alpha 1 and alpha 2, of postsynaptic alpha-adrenoceptors in the vasculature of rabbits. It seems that phenylephrine produces pressor responses by acting alpha 1-type adrenoreceptors: small doses of norepinephrine by acting on alpha 2-type: large doses of norepinephrine by acting on both types.
Labetalol ; Moxisylyte ; Muscle, Smooth, Vascular ; Norepinephrine* ; Phentolamine ; Phenylephrine* ; Piperoxan ; Prazosin ; Rabbits ; Yohimbine

PURPOSE: It is known that alpha-2 receptor is found at the presynaptic serotonergic nervous system and a consequence of increased activation of alpha-2 receptor decreases the serotonin release. So Alpha-2 blockers may have the effect on the release of serotonin. The major serotonergic innervation is found at the hippocampus. This study was performed to investigate the effect of the alpha-2 receptor blocker to serotonin release in rat hippocampus. MATERIALS AND METHODS: The hippocampus from the male rat brain was sliced. After 30 minutes preincubation in the normal buffer, the slices were incubated for 20 minutes in a buffer containing 0.1 microM[3H]5-HT for uptake, and washed. After administration of alpha 2 receptor blockers, yohimbine (10-5M), the release of [3H]5-HT into the buffer was measured, the radioactivities in each buffer and the tissue were counted and the results were expressed as a percentage of the total activity. The value of released [3H]5-HT was expressed as percent of the value at 50 minutes when a steady state of [3H]5-HT release was obtained. RESULTS: After adminstration of yohimbine (10-5M), the values(mean+/-SE, %) were 147.5+/-9.2 at 60 minutes and 143.8+/-7.3 at 70 minutes compared to the values of control group, 96.6+/-1.9 at 60 minutes and 89.6+/-2.3 at 70 minutes. The release was increased significantly after adminstration of yohimbine. CONCLUSIONS: Alpha-2 receptor blockers increased the release of serotonin. It is suggested that the consideration of the increase of serotonin release by alpha-2 receptor blockers may be helpful to understand the effect of serotonin on sexual function.
Animals ; Brain ; Hippocampus ; Humans ; Male ; Nervous System ; Radioactivity ; Rats* ; Serotonin* ; Yohimbine

BACKGROUND: Clonidine, an alpha2 adrenoceptor agonist, has been known to have antinociceptive and antiallodynic effects. The antinociceptive and antiallodynic effects of brimonidine, a new selective alpha2 agonist, have not been evaluated yet in rats. Behavioral tests were performed to investigate the effects of systemically and spinally administered brimonidine on nociception and mechanical allodynia and the effect of spinal nerve ligation (SNL) on antinociception. METHODS: Rats were prepared with tight ligation of spinal nerves and/or a lumbar intrathecal catheter implantation. Using a hot plate (HP) test or von Frey hair (VFH) test, the effect of intraperitoneal (I.P.) and intrathecal (I.T.) brimonidine in normal and SNL rats were examined. I.P. brimonidine (100 - 1,000 microgram) and I.T. brimonidine (0.1 - 3.0 microgram) were given to examine the antinociceptive effect on an HP test. After a SNL, a HP test was conducted at the same doses of brimonidine to compare with the preoperative state. I.T. brimonidine (0.03 - 3.0 microgram) and saline (control) were administered to examine the antiallodynic effect in SNL rats. In addition, an antagonistic study with yohimbine 1.0 mg/kg I.P. was performed to investigate the reversal of the antiallodynic effect of brimonidine. Allodynic thresholds for lesioned hindpaw withdrawl to a VFH test were assessed and converted to %MPE. RESULTS: I.P. brimonidine produced an antinociceptive effect, and I.T. brimonidine also produced a significant antinociceptive effect (P < 0.05). After an SNL, I.T. brimonidine produced a dose-dependent antinocicpetive effect. In addition, I.T. brimonidine produced a dose-dependent antiallodynic effect which is antagonized by yohimbine (P < 0.05). CONCLUSIONS: The results suggest that brimonidine has a more potent antiallodynic effect when given intrathecally.
Adrenergic Agonists* ; Animals ; Catheters ; Clonidine ; Hair ; Hyperalgesia ; Ligation ; Nociception ; Rats ; Spinal Nerves ; Yohimbine ; Brimonidine Tartrate

Previous studies have suggested that brain stem noradrenergic inputs differentially modulate neurons in the paraventricular nucleus (PVN). Here, we compared the effects of norepinephrine (NE) on spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) in identified PVN neurons using slice patch technique. In 17 of 18 type I neurons, NE (30-100microM) reversibly decreased sIPSC frequency to 41+/-7% of the baseline value (4.4+/-0.8 Hz, p<0.001). This effect was blocked by yohimbine (2-20microM), an alpha2-adrenoceptor antagonist and mimicked by clonidine (50 microM), an alpha2-adrenoceptor agonist. In contrast, NE increased sIPSC frequency to 248+/-32% of the control (3.06+/-0.37 Hz, p<0.001) in 31 of 54 type II neurons, but decreased the frequency to 41+/-7% of the control (5.5+/-1.3 Hz) in the rest of type II neurons (p<0.001). In both types of PVN neurons, NE did not affect the mean amplitude and decay time constant of sIPSCs. In addition, membrane input resistance and amplitude of sIPSC of type I neurons were larger than those of type II neurons tested (1209 vs. 736 M omega, p<0.001; 110 vs. 81 pS, p<0.001). The results suggest that noradrenergic modulation of inhibitory synaptic transmission in the PVN decreases the neuronal excitability in most type I neurons via alpha2-adrenoceptor, however, either increases in about 60% or decreases in 40% of type II neurons.
Brain Stem ; Clonidine ; Inhibitory Postsynaptic Potentials* ; Membranes ; Neurons ; Norepinephrine ; Paraventricular Hypothalamic Nucleus* ; Synaptic Transmission ; Yohimbine