The effects of intraventricular atropine on the heart rate was investigated in the rabbit. Intraventricular administration of atropine in a dose of 10, 30, 100, or 300 ug produced dose dependant bradycardia. Atropine (100 ug) induced bradycardia was abolished by bilateral vagotomy or intravenous atropine, and inhibited by intravenous propranolol but not by intravenous Regitine. Intraventricular Ecolid or regitine pretreatment diminished the bradycardia induced by intraventricular atropine. From the above results, it is suggested that a central adrenergic mechanism as well as vagal activity plays an important role in the intraventricular atropine-induced bradycardia.
Atropine* ; Bradycardia ; Chlorisondamine ; Heart Rate* ; Heart* ; Phentolamine ; Propranolol ; Vagotomy

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

The effect of Pheniramine(Avil), a histaminergic-1 receptor blocking agent presently employed in treating various allergic diseases on pressor actions of norepinephring(NE) and tyramine (TR) was studied in the rabbit. Pheniramine, when given into a femoral vein with a dose(3mg/kg) enough to block H1-receptor, potentiated markedly the pressor responses of NE and TR. The pressor action of NE augmented by pheniramine was not affected by additional adminstration of debrisoquin (Drenergic neuron blocker) or phenelzine(monoamine oxidase inhibitor) or desipramine(U1-uptake blocker), or while potentiated by additional treatment with chlorisondamine(ganglionic blocker)or reserpine(catecholamine depleter). The hypertensive response of NE to phenelzine or desipramine was reinforced significantly by addition of pheniramine, but the response of NE in rabbits treated with reserpine or chlorisondamine or debrisoquin was not influenced by pheniramine-addition. Elevation of blood pressure to TR potentiated by pheniramine was attenuated significantly by reserpine treatment with chlorisondamine made the significant augmentation of pressor action to TR after pheniramine. Tyramine-induced response of blood pressure after pheniramine, but the response of blood pressure to TR caused by phenelzine or desipramine was enhanced markedly by pheniramine-treatment. From the above experimental results, it is thought that the pressor effect of NE and TR potentiated by pheniramine is similar to that of debrisoquin, i.e. the sensitization of effector cell, and that central action of pheniramine can not ruled out.
Blood Pressure ; Chlorisondamine ; Debrisoquin ; Desipramine ; Femoral Vein ; Neurons ; Norepinephrine* ; Oxidoreductases ; Phenelzine ; Pheniramine ; Rabbits ; Reserpine ; Tyramine*

This study is an attempt to investigate the effect of total Ginseng saponin (GTS) on the blood pressure of the rat and to elucidate its mechanism of action. GTS, when injeced into a femoral vein of the rat, caused dose-related fall in blood pressure with secondarily elevation of the blood pressure. The depressor effect of GTS was blocked by treatment of atropine and prazosin, but not affected by pretreatment with chlorisondamine or cyproheptadine. GTS inhibited significantly the pressor response evoked by norepinephrine. The pressor effect of GTS was not affected by treatment with atropine or cyproheptadine, but was attenuated markedly by pretreatment with chlorisondamine. From the above mentioned results, it is thought that GTS produces the pressor and the depressor actions in the rat, and that its depressor response is exerted partly through the stimulation of cholinergic muscaric receptors with the blockade of adrenergic alpha-receptors, and that its pressor response is revealed by stimulation of nicotinic receptors in autonomic ganglia.
Animals ; Atropine ; Blood Pressure* ; Chlorisondamine ; Cyproheptadine ; Femoral Vein ; Ganglia, Autonomic ; Norepinephrine ; Panax* ; Prazosin ; Rats* ; Receptors, Adrenergic, alpha ; Receptors, Nicotinic ; Saponins*

The present study was attempted to investigate the characteristics of epibatidine on secretion of catecholamines (CA) from the isolated perfused model of the rat adrenal gland, and to establish the mechanism of action. Epibatidine (3X10(-8) M) injected into an adrenal vein produced a great inhibition in secretory response of CA from the perfused rat adrenal gland. However, upon the repeated injection of epibatidine (3X10(-8) M) at 15 min-intervals, CA secretion was rapidly decreased after second injection of epibatidine. However, there was no statistical difference between CA secretory responses of both 1st and 2nd periods by the successive administration of epibatidine at 120 min-intervals. Tachyphylaxis to releasing effects of CA evoked by epibatidine was observed by the repeated administration. Therefore, in all subsequent experiments, epibatidine was not administered successively more than twice only 120 min-intervals. The epibatidine-induced CA secretion was markedly inhibited by the pretreatment with atropine, chlorisondamine, pirenzepine, nicardipine, TMB-8, and perfusion of Ca2+/-free Krebs solution containing EGTA, while was not affected by diphenhydramine. Moreover, the CA secretion evoked by ACh for 1st period (0apprx4 min) was greatly potentiated by the simultaneous perfusion of epibatidine (1.5X10(-8) M), but followed by time-dependently gradual reduction after 2nd period. The CA release evoked by high potassium (5.6+/-10(-8) M) for 1st period (0apprx4 min) was also enhanced by the simultaneous perfusion of epibatidine, but those after 2nd period were not affected. Taken together, these experimental data suggest that epibatidine causes catecholamine secretion in a calcium dependent fashion from the perfused rat adrenal gland through activation of neuronal cholinergic (nicotinic and muscarinic) receptors located in adrenomedullary chromaffin cells. It also seems that epibatidine-evoked catecholamine release is not relevant to stimulation of histaminergic receptors.
Adrenal Glands* ; Animals ; Atropine ; Calcium ; Catecholamines ; Chlorisondamine ; Chromaffin Cells ; Diphenhydramine ; Egtazic Acid ; Neurons ; Nicardipine ; Perfusion ; Pirenzepine ; Potassium ; Rats* ; Tachyphylaxis ; Veins

It is well documented that elevation of intracranial pressure is accompanied by arterial blood pressure(cushing response) in laboratory animals as well as in human. When the elevation of intracranial pressure(ICP) was repeated in a rabbit at an interval of 30-60 min, the blood pressure increased more promtly than in the first elevation of ICP, suggesting that mechanism involved in the pressure might be different. Therefore, this study was undertaken to clarify the pharmacological characteristics of the response to the first and repeated(second) elevation of ICP in urethane anesthetized rabbits. Increasing ICP, induced by infusion of saline into a ballooned in the epidural space, produced arise of the arterial blood pressure. When the blood pressure reached a peak, the balloon was suddenly deflated to reduced the ICP and blood pressure declined (the first ICP elevation experiment). After 30-60 min the same procedure was repeated (the second ICP-elevation experiment) Results are summarized as follows; 1) In the first ICP elevation experiment, the arise of ICP was relatively slow at the beginning of the infusion but became sharp as the infusion proceeded. When ICP increased sharply BP also increased abruptly and heart rate decreased. 2) In the second ICP elevation experiment, the slight decrease in BP which appeard at the beginning of the first ICP elevation experiment rat observed, so that only an abrupt arise of BP was seen. 3) Intravenous chlorisondamine inhibited the pressure responses in the second ICP elevation experiment. 4) Intraventricular corynanthine had little effect on the pressure response to the first ICP elevation but inhibited the pressure response to the second ICP elevation. 5) Intraventricular clonidine, yohimbine and prazosin little effect on the pressure response to the second ICP elevation. From this results that functional integrity of central alpha 2-adrenoceptor which took part in the pressure response to the first ICP elevation might have deranged in the second ICP elevation and that central alpha 1-adrenoceptors play a dominant role in the pressure response to the second ICP elevation.
Animals ; Animals, Laboratory ; Arterial Pressure ; Blood Pressure ; Chlorisondamine ; Clonidine ; Epidural Space ; Heart Rate ; Humans ; Intracranial Pressure* ; Prazosin ; Rabbits ; Rats ; Urethane ; Yohimbine

Changes of blood pressure, heart rate, ECG, respiration rate and pupil size by intracerebroventricular(ICV) infusion of hypertonic NaCl with 0.04 ml/min for 5 min(total 0.2ml) were observed in urethane-anesthetized rabbits. ICV infusion of 0.75M NaCl produced slight pressor effect (11mmHg) and did not affect other parameters. ICV infusion of 1.5M NaCl began to increase blood pressure from 2~3 min after the infusion and produced maximal increase(24mmHg) at 5~10 min. Then the pressor effect was recovered to the original level at 30~60 min. Change of heart rate by the infusion was not clear, but ST-segment of ECG was markedly depressed. Respiration rate increased about 1.5 times than the control in accordance with the pressor effect and the state was continued even after the recover of the pressor effect. Both pupils dilated markedly and light-reflex was lost. Changes of parameters by ICV infusion of 3.0M NaCl were similar to those by 1.5M NaCl and some rabbits caused severe arrhythmias and died. The purpose of present study is to investigate the mechansim(s) of the pressor effect induced by the ICV infusion of 1.5M NaCl. The pressor effect of 1.5M NaCl was attenuated by the continuous infusion of vasopressin antagonist(20microm/kg/min) but not affected by intravenous treatment with 2mg/kg phentolamine, 2mg/kg propranolol and 1mg/kg chlorisondamine. The pressor effect was not altered with ICV 0.12mg/kg phenoxybenzamine, 0.4mg diltiazem, 0.1mg/kg mecamylamine and 0.2mg/kg atropine. After ICV infusion of 25microg/kg/min of diazepam, however, the pressor effect was completely abolished and restored 3~4 hours after stopping diazepam infusion. The pressor effect was rather potentiated than inhibited in bilateral adrenalectomized or nephrectomized rabbits. Infusion of 2microg/kg/min of saralasin for 10 min in the bliateral adrenalectomized rabbit did not affect the pressor effect at all. These results suggest that hypertensive effect induced by ICV infusion of hypertonic NaCl is mediated by the increase of vasopressin secretion.
Arrhythmias, Cardiac ; Atropine ; Blood Pressure ; Chlorisondamine ; Diazepam ; Diltiazem ; Electrocardiography ; Heart Rate ; Infusions, Intraventricular* ; Mecamylamine ; Phenoxybenzamine ; Phentolamine ; Propranolol ; Pupil ; Rabbits* ; Respiratory Rate ; Saralasin ; Vasopressins

The present study was designed to investigate the characteristics of gintonin, one of components isolated from Korean Ginseng on secretion of catecholamines (CA) from the isolated perfused model of rat adrenal gland and to clarify its mechanism of action. Gintonin (1 to 30 µg/ml), perfused into an adrenal vein, markedly increased the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. The gintonin-evoked CA secretion was greatly inhibited in the presence of chlorisondamine (1 µM, an autonomic ganglionic bloker), pirenzepine (2 µM, a muscarinic M₁ receptor antagonist), Ki14625 (10 µM, an LPA₁/₃ receptor antagonist), amiloride (1 mM, an inhibitor of Na⁺/Ca²⁺ exchanger), a nicardipine (1 µM, a voltage-dependent Ca²⁺ channel blocker), TMB-8 (1 µM, an intracellular Ca²⁺ antagonist), and perfusion of Ca²⁺-free Krebs solution with 5mM EGTA (a Ca²⁺chelater), while was not affected by sodium nitroprusside (100 µM, a nitrosovasodialtor). Interestingly, LPA (0.3~3 µM, an LPA receptor agonist) also dose-dependently enhanced the CA secretion from the adrenal medulla, but this facilitatory effect of LPA was greatly inhibited in the presence of Ki 14625 (10 µM). Moreover, acetylcholine (AC)-evoked CA secretion was greatly potentiated during the perfusion of gintonin (3 µg/ml). Taken together, these results demonstrate the first evidence that gintonin increases the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. This facilitatory effect of gintonin seems to be associated with activation of LPA- and cholinergic-receptors, which are relevant to the cytoplasmic Ca²⁺ increase by stimulation of the Ca²⁺ influx as well as by the inhibition of Ca²⁺ uptake into the cytoplasmic Ca²⁺ stores, without the increased nitric oxide (NO). Based on these results, it is thought that gintonin, one of ginseng components, can elevate the CA secretion from adrenal medulla by regulating the Ca²⁺ mobilization for exocytosis, suggesting facilitation of cardiovascular system. Also, these findings show that gintonin might be at least one of ginseng-induced hypertensive components.
Acetylcholine ; Adrenal Glands ; Adrenal Medulla* ; Amiloride ; Animals ; Cardiovascular System ; Catecholamines ; Chlorisondamine ; Cytoplasm ; Egtazic Acid ; Exocytosis ; Ganglia, Autonomic ; Nicardipine ; Nitric Oxide ; Nitroprusside ; Panax ; Perfusion ; Pirenzepine ; Rats ; Veins

Kanagawa hemolysin (KH), an exotoxin produced from Kanagawa phenomenon-positive Vibrio parahemolyticus, has been shown to possess various biological activities including hemolysis, enterotoxicity, cytotoxicity, and cardiotoxicity. The aim of this study was to investigate the effect of KH on the cardiovascular system and its mechanism, employing in vivo and in vitro experiments of the rat. Intracerebroventricular (icv) administration of 100 mHU KH produced a marked and continuous pressor effect (icv KH-pressor effect), and the icv pressor effect was not repeatable. However, intravenous (iv) injection of the same dose of KH induced a prominent depressor effect (iv KH-depressor effect). The icv KH-pressor effect was inhibited by acid-denaturation, while the iv KH-depressor effect was not. Simultaneous icv administration of the three agents (ouabain, diltiazem, or bumetanide: 10ng/kg each) significantly reduced the pressor effect. The icv KH-pressor effect was inhibited by treatment with iv phentolamine or chlorisondamine, but was not affected by iv candesartan. The iv KH-depressor effect was repeatable and was attenuated by treatment with iv NAME or methylene blue. In vitro experiments using isolated thoracic aorta, 10(-6) M phenylephrine (PE) and 50 mM KCl produced a sustained contraction. In rings contracted with either agents, KH showed relaxant responses in a concentration- dependent fashion and the relaxation (KH-vasorelaxation) was not dependent on the existence of the endothelium. The KH-vasorelaxation in the endothelium-intact rings contracted by PE was abolished by methylene blue treatment. In summary, the present findings suggest that in the icv KH-pressor effect the cation leak-inducing action of KH is implicated, which leads to the increased central sympathetic tone, that the iv KH-depressor effect results from the vasorelaxation via NO-guanylate cyclase system, and that the KH-vasorelaxation is independent of the endothelium and the guanylate cyclase system is involved in it. In conclusion, the mechanism of KH producing the icv pressor effect may not be identical to that of KH producing the iv depressor effect.
Animals ; Aorta ; Aorta, Thoracic ; Blood Pressure* ; Bumetanide ; Cardiovascular System ; Chlorisondamine ; Diltiazem ; Endothelium ; Exotoxins ; Guanylate Cyclase ; Hemolysis ; Ion Transport ; Methylene Blue ; Phentolamine ; Phenylephrine ; Rats* ; Relaxation ; Vasodilation ; Vibrio

The present study was attempted to investigate the effect of vasoactive intestinal polypeptide (VIP) on secretion of catecholamines (CA) and to establish whether there is the existence of a noncholinergic mechanism in adrenomedullary CA secretion from the isolated perfused rat adrenal gland. The perfusion into an adrenal vein of VIP (3 X 10-6 M) for 5 min or the injection of acetylcholine (ACh, 5.32 X 10-3 M) resulted in great increases in CA secretion. Tachyphylaxis to releasing effect of CA evoked by VIP was not observed by the repeated perfusion. The net increase in adrenal CA secretion evoked by VIP still remained unaffected in the presence of atropine or chlorisondamine. However, the CA release in response to ACh was greatly inhibited by the pretreatment with atropine or chlorisondamine. The releasing effects of CA evoked by either VIP or ACh were depressed by pretreatment with nicardipine, TMB-8, and the perfusion of Ca2+-free medium. Moreover, VIP- as well as ACh-evoked CA secretory responses were markedly inhibited under the presence of (Lys1, Pro2.5, Arg3.4, Tyr6)-VIP or naloxone. CA secretory responses induced by ACh and high K+ (5.6 X 10-2 M) were potentiated by infusion of VIP (3 X 10-6 M for 5 min). Taken together, these experimental results indicate that VIP causes CA release in a fashion of calcium ion-dependence, suggesting strongly that there exists a noncholinergic mechanism that may be involved in the regulation of adrenomedullary CA secretion through VIP receptors in the rat adrenal gland, and that VIP may be the noncholinergic excitatory secretagogue present in the chromaffin cells.
Acetylcholine ; Adrenal Glands ; Adrenal Medulla* ; Animals ; Atropine ; Calcium ; Catecholamines ; Chlorisondamine ; Chromaffin Cells ; Naloxone ; Nicardipine ; Perfusion ; Rats* ; Receptors, Vasoactive Intestinal Peptide ; Tachyphylaxis ; Vasoactive Intestinal Peptide ; Veins