• The Korean Journal of Physiology
• /
• v.23 no.1
• /
• pp.99-108
• /
• 1989

The effects of prostaglandin $(PGF_{2{\alpha}})$ on the contractility of vascular smooth muscle were investigated in the helical strip of the rabbit aorta. The aortic strip was immersed in the phosphate-buffered Tyrode's solution which was equilibrated with 100% $O_{2}$ at $35^{\circ}C$ and its isometric tension was measured. The contraction was induced by $(PGF_{2{\alpha}})$, norepinephrine (NE), or potassium (40 mM) in the nomal Tyrode's solution (1 mM, $Ca^{2+}$) or $Ca^{2+}-free$ Tyrode's solution. Effects of verapamil and phentolamine on the contraction were also observed. The aortic strip began to contract at the concentration of $5\;{\mu}g%$ and reached the maximal contraction at the concentration of $150\;{\mu}g%$ $(PGF_{2{\alpha}})$. The maximal contraction was corresponded respectively to $52.2{\pm}3.0%$ and $81.5{\pm}3.5%$ of maximal contraction by NE $(1{\times}10^{-5}M)$ and 40 mM $K^{+}$. And the maximal contractions by $(PGF_{2{\alpha}})$ or NE were induced at the concentration of about 1 mM $Ca^{2+}$. $(PGF_{2{\alpha}})$ induced the contraction of aortic strip even after induction of contraction by 40 mM $K^{+}$ and the contraction by $(PGF_{2{\alpha}})$ was not blocked by the ${\alpha}-receptor$ blocker, phentolamine. And the contraction by the $(PGF_{2{\alpha}})$ was inhibited partially by a verapamil at the concentration of $1{\times}10^{-5}M$ and the contraction began to increase at the concentration of $1{\times}10^{-4}M$ verapamil. Whereas the contraction by NE was completely blocked by verapamil. Though both the $(PGF_{2{\alpha}})$ and NE induced the contraction in the $Ca^{2+}-free$ Tyrode's solution, the peak tension was not maintained. But the rate of tension decline was lower in the contraction by $(PGF_{2{\alpha}})$ than in that by NE. The verapamil did not inhibit the contraction by $(PGF_{2{\alpha}})$ in the $Ca^{2+}-free$ Tyrode's solution and increased the contraction at the concentration of above $1{\times}10^{-4}M$. The NE-induced contraction in the $Ca^{2+}-free$ Tyrode's solution was inhibited completely by a verapamil. From the above results it is suggested that the contraction induced by $(PGF_{2{\alpha}})$ results from the promotion of the both $Ca^{2+}$ influx and the intracellular $Ca^{2+}$ release by different way from NE.

• Journal of Chest Surgery
• /
• v.23 no.3
• /
• pp.452-464
• /
• 1990

It is well known that extracellular Calcium plays a very important role in several steps of smooth muscle excitability and contractility, and there have been many concerns about factors influencing the distribution of extracellular Ca++ and the Ca++ flux through the cell membrane of the smooth muscle. Based on the assumption that Mg++ may also play an important role in the excitation and contraction processes of the smooth muscle by taking part in affecting Ca++ distribution and flux, many researches are being performed about the exact role of Mg++, especially in the vascular smooth muscle. But yet the effect of Mg++ in the smooth muscle activity is not clarified, and moreover the mechanism of Mg++ action is almost completely unknown. Present study attempted to clarify the effect of Mg++ on the excitability and contractility in the multiunit and unitary smooth muscle, and the mechanism concerned in it. The preparations used were the guinea-pig aortic strip as the experimental material of the multiunit smooth muscle and the rat uterine strip as the one of the unitary smooth muscle. The tissues were isolated from the sacrificed animal and were prepared for recording the isometric contraction. The effects of Mg++ and Ca++ were examined on the electrically driven or spontaneous contraction of the preparations. And the effects of these ions were also studied on the K+ or norepinephrine contracture. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% 02 and kept at 35oC. The results obtained were as follows: 1] Mg++ suppressed the phasic contraction induced by electrical field stimulation dose-dependently in the guinea-pig aortic strip, while the high concentration of Ca++ never recovered the decreased tension. These phenomena were not changed by the a - or b - adrenergic blocker. 2]Mg++ played the suppressing effect on the low concentration [20 and 40 mM] of K+-contracture in the aortic muscle, but the effect was not shown in the case of 100mM K+-contracture. 3] Mg++ also suppressed the contracture induced by norepinephrine in the aortic preparation. And the effect of Mg++ was most prominent in the contracture by the lowest [10 mM] concentration of norepinephrine. 4] In both the spontaneous and electrically driven contractions of the uterine strip, Mg++ decreased the amplitude of peak tension, and by the high concentration of Ca++ the amplitude of tension was recovered unlike the aortic muscle. 5] The frequency of the uterine spontaneous contraction increased as the [Ca++] / [Mg++] ratio increased up to 2, but the frequency decreased above this level. 6] Mg++ decreased the tension of the low[20 and 40mM] K+-contracture in the uterine smooth muscle, but the effect did not appear in the 100mM K+-contracture. From the above results, the following conclusion could be made. 1] Mg++ seems to suppress the contractility directly by acting on the smooth muscle itself, besides through the indirect action on the nerve terminal, in both the aortic and uterine smooth muscles. 2] The fact that the depressant effect of Mg++ on the K+-contracture is in inverse proportion to an increase of K+ concentration appears resulted from the extent of the opening state of the Ca++ channel. 3] Mg++ may play a depressant role on both the potential dependent and the receptor-operated Ca++ channels. 4] The relationship between the actions of Mg++ and Ca++ seems to be competitive in uterine muscle and non-competitive in aortic strip.

• The Journal of Korean Medicine
• /
• v.19 no.2
• /
• pp.50-58
• /
• 1998

The effects of the Evodiae fructus on the cardiovascular function were assessed in spontaneously hypertensive rats, and isolated preparation of spontaneously hypertensive rats aortic strip. In spontaneously hypertensive rats, intraperitoneal administration of methanol crude extract of Evodiae Fructus (0.5mg/kg) lowered aterial blood pressure which lasted for at least 4 hours. The hypotensive effect of Evodiae Fructus was more stronger with ${\alpha}-adrenoreceptor$ inhibitor(Phentholamine) and it was not affected by ${\beta}-adrenoreceptor$ inhibitor(Propranolol). The hypotensive effect of Evodiae Fructus was abolished by NAME. It is suggested that the hypotensive effect of Evodiae Fructus may be concern with endothelium-derived relaxing factor and it may be mediated through NO synthesis. Evodiae Fructus showed a vasorelaxing effect on denude aortic strip. It is suggested that Evodiae Fructus has a direct relaxing effect on vascular smooth muscle cells. Judging from above results, it was proved that hypotensive effect of Evodiae Fructus. The mechanism of hypotensive action may be concern with endothelium-derived relaxing factor and direct relaxing effect on vascular smooth muscle cells. Therefore, it is suggested that Evodiae Fructus is applicable to hypertension.

• Journal of Chest Surgery
• /
• v.24 no.3
• /
• pp.229-244
• /
• 1991

A bioassay technique and organ bath study were performed to analyze the effects of extracellular $Ca^{2+}$ and $Ca^{2+}$-antagonists on endothelium-derived relaxing factor[s][EDRF] released from the endothelial cells of rabbit aorta. Transverse strips with intact endothelium or damaged endothelium were used for the mechanical contraction experiment using organ bath. Long segment including thoracic and abdominal aorta with endothelium [EDRF donor aorta] was perfused with Tyrode solution which was aerated with 95% $O_2-5%$ $CO_2$ mixed gas and kept at 35oC. The perfusate was bioassayed with a transverse strip of thoracic aorta with damaged endothelium. The test strip was contracted with nor-epinephrine and acetylcholine was used to stimulate the release of EDRF from endothelial cells. The results obtained were as follows; 1] The endothelium-dependent relaxation[EDR] induced by acetylcholine was biphasic; an initial rapid relaxation followed by a slow relaxation. 2] EDR induced by acetylcholine was reduced gradually with the decrease in the concentration of extracellular $Ca^{2+}$. The effect of extracellular $Ca^{2+}$ on EDR was more prominent in the late slow relaxation phase. 3] EDR to acetylcholine was not altered by acute exposure to organic $Ca^{2+}$-antagonists. Pretreatment with verapamil to the EDRF donor aortic segment did not alter the magnitude of EDR. 4] Among the inorganic $Ca^{2+}$-antagonists $Mn^{2+}$ and $Cd^{2+}$ did not inhibit EDR, whereas $Co^{2+}$ and $La^{3+}$ inhibited EDR. 5] The inhibitory response of $Co^{2+}$ to EDR developed when infused directly on the test strip. That of $La^{3+}$, however, was evoked when added to solution perfusing the donor aortic segment. The above results suggest that $Ca^{2+}$-antagonists do not affect EDR and the inhibitory effect of $Ca^{2+}$ results from influencing the action of EDRF on vascular smooth muscle, whereas that of $La^{3+}$ results from its action on the release of EDRF from endothelial cells.

• Biomolecules & Therapeutics
• /
• v.13 no.1
• /
• pp.48-58
• /
• 2005

The present study was conducted to investigate the effects of nicorandil on arterial blood pressure and vascular contractile responses in the normotensive anesthetized rats and to establish the mechanism of action. Nicorandil (30~300 ${\mu}g/kg$) given into a femoral vein of the normotensive anesthetized rat produced a dose-dependent depressor response. These nicorandil-induced hypotensive responses were not affected by pretreatment with atropine (3.0 mg/kg, i.v.) or propranolol (2.0 mg/kg, i.v.), while markedly inhibited in the presence of chlorisondamine (1.0 mg/kg, i.v.) or phentolamine (2.0 mg/kg, i.v.). Futhermore, after the pretreatment with 4-aminopyridine (1.0 mg/kg/30 min, i.v.) or glibenclamide (50.0 ${\mu}g/kg$/30min) into a femoral vein made a significant reproduction in pressor responses induced by intravenous norepinephrine. In he isolated rat aortic strips, both phenylephrine (10$^{-5}$ M)- and high potassium (5.6 ${\times}\;10^{-2}$ M)-inducedcontractile responses were dose-dependently depressed in the presence of nicorandil (25~100 ${\mu}M$). Collectively, these experimental results demonstrate that intravenous nicorandil causes a dose-dependent depressor action in the anesthetized rat at least partly through the blockade of vascular adrenergic ${\alpha}_1$-receptors, in addition to the well-known mechanism of potassium channel opening-induced vasorelaxation.

• The Korean Journal of Pharmacology
• /
• v.28 no.1
• /
• pp.75-79
• /
• 1992

Higenamine, which is one of active component of Aconiti tuber, has been known to have positive inotropic effect through adrenergic beta-receptor. The effect of higenamine on norepinepharine or potassium induced contraction of pulmonary aorta in rabbit were studies. 1. The contraction of aortic strips induced by norepinephrine was suppressec by pre-or post-treatment of higenamine dose dependently and those effects of higenamine were prevented by propranolol. The $pA_2$ value of higenamine against propranolol calculated as 8.25. 2. The effect of higenamine was not affected by phentolamine. 3. Isoprotrenol has shown 10 times stronger vasodiatory effect on norepinephrine induced cntracture than that of higenamine but high concentration $(3.3{\times}10^{-6}\;M)$ of isoproterenol produce intrinsic activity. 4. Vasodilatory effect of higenamine or isoproterenol was not observed in potassium induced contacture of pulmonary aortic strips. These results strongly suggest that higenamine dilated the pulmonary vascular smooth muscle through stimulation of adrenergic beta-receptor.

• Proceedings of the Ginseng society Conference
• /
• 1980.09a
• /
• pp.71-76
• /
• 1980

Aortic strips were prepared from rabbits, and the tensions were maintained by administration of norepinephrine into the incubation chamber. The application of diol or triol induced relaxation of the aortic strip, as indicated by the decreased aortic tension. Triol, in a concentration of $30\;mg\%\;causes\;approximately\;50\%$ of muscle relaxation, whereas a similar degree of relaxation is induced by $50\;mg\%$ of diol. This indicates that both triol and diol cause relaxation of the aorta, but that triol is about $170\%$ more potent than diol. It is well established that blood-vessel smooth-muscle tone is regulated by the available intracellular $Ca^{++}$ concentration, which in turn is profoundly influenced by interaction of the cellular membrane and sarcoplasmic reticulum in the smooth muscle. Thus, any agent which modifies the smooth-muscle tone is expected to interfere with the $Ca^{++}$ binding or uptake of sarcolemma and sarcoplasmic reticulum. In the following experiments sarcoplasmic reticulum and sarcolemma were prepared from the ventricle of rabbit heart, and the active $Ca^{++}$ uptake by these cellular components was measured employing $Ca^{45}$ in the presence of triol and diol. It was found that the active $Ca^{++}$ uptake in the presence of ATP by sarcoplasmic reticulum was inhibited by both triol and diol. Panaxatriol, in a concentration of $80\;mg\;\%,$ inhibited $Ca^{++}$ uptake by $30\%,$ whereas panaxatriol in the same concentration inhibited uptake by $20\%.$ It is clear that triol is a more potent inhibitor of active $Ca^{++}$ transport in sarcoplasmic reticulum than diol. The $Ca^{++}$ binding of the cellular membrane was also studied employing Ca45 and milipore techniques. It was found that triol in a concentration of $80\;mg\;\%,$ decreased $Ca^{++}$ binding by $29\%.$ Diol in the same concentration decreased the binding by $17\%.$ It is clear that both triol and diol inhibit $Ca^{++}$ binding to the cellular membrane, but triol is approximately $180\%$ more potent than diol.

• Journal of Sensor Science and Technology
• /
• v.20 no.5
• /
• pp.343-350
• /
• 2011

The compliance and stiffness of artery are closely related with disease of arteries. Pulse wave velocity(PWV) in the blood vessel is a basic and common parameter in the hemodynamics of blood pressure and blood flow wave traveling in arteries because the PWV is affected directly by the conditions of blood vessels. However, there is no standardized method to measure the PWV and it is difficult to measure. The conventional PWV measurement has being done by manual calculation of the pulse wave transmission time between coronary arterial proximal and distal points on a strip chart on which the pulse wave and ECG signal are recorded. In this study, a pressure sensor consisting of strain gauges is used to measure the blood pressure of arteries in invasive method and regular ECG electrodes are used to record the ECG signal. The R-peak point of ECG is extracted by using a reference level and time windowing technique and the ascending starting point of blood pressure is determined by using differentiation of the blood pressure signal and time windowing technique. The algorithm proposed in this study, which can measure PWV automatically, shows robust and good results in the extraction of feature points and calculation of PWV.

• The Korean Journal of Pharmacology
• /
• v.11 no.2
• /
• pp.19-27
• /
• 1975

Haloperidol, a butyrophenone, was synthetized by Janssen and introduced for the treatment of psychosis. Although structurally different from the phenothiazines, the butyrophenones share many of their pharmacological properties, such as inhibition of conditioned avoidance response, blocking effect of amphetamine reaction, producing catalepsy, antishock effect and protection against the lethal effects of catecholalmines. Chlorpromazine can lower the arterial blood pressure through its adrenergic blocking activity, its direct effect in relaxing vascular smooth muscle, its direct effect in depressing the myocardium and its action in a complex manner on the central nervous system. In the case of haloperidol, however, was not clarified the mechanism of lowering the blood pressure. The present paper describes the effects of haloperidol on cardiovascular system to investigate the mechanisms of its actions on the arterial blood pressure. The results are followings; 1. In anesthetized cats, intravenous administration of haloperidol and chlorpromazine in the dose of 0.1mg/kg produced a slight decrease in the blood pressure, which followed by complete recovery within $30{\sim}60$ minutes. In the dose of 3mg/kg, however, both produced an abrupt and marked decrease of the blood pressure, which followed by delayed recovery. 2. Haloperidol in the dose ranges of 0.1mg to 3.0mg/kg tended to produce the heart rate slowing in the cats, while chlorpromazine has no effect on the rate. 3. Following administration of haloperidol or chlorpromazine, epinephrine reversal in the arterial blood pressure was observed in the cat, however the responses of norepinephrine and acetylcholine were little affected. 4. In the isolated rabbit atrium the contractility was depressed by haloperidol in the doses over 0.5mg per 100ml, but the rate was not affected. In contrast, the epinephrine-induced contractility was not depressed after haloperidol treatment. However, the increased rate of atrium by epinephrine was partially blocked after haloperidol. 5. In the isolated rabbit aortic strip, epinephrine-induced contraction was blocked by haloperidol. With the above results, it may be concluded that the hypotensive effect of haloperidol was largely due to ${\alpha}$-adrenergic blocking properties and the direct effect in depressing the myocardium as well as its action on central nervous system.

• The Korean Journal of Pain
• /
• v.27 no.3
• /
• pp.229-238
• /
• 2014

Background: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endothelium-denuded rat aortas precontracted with phenylephrine. Methods: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ($[Ca^{2+}]_i$) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. Results: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced $[Ca^{2+}]_i$ decrease in the aortas precontracted with phenylephrine. Conclusions: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine-induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.