• Biomolecules & Therapeutics
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• v.11 no.2
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• pp.119-125
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• 2003

The present study was conducted to investigate the effects of bornyl acetate on arterial blood pressure and vascular contractile responses in the normotensive rats and to establish the mechanism of action. Both phenylephrine (an adrenergi$\alpha$-receptor agonist) and high potassium (a membrane-depolarizing agent) caused greatly contractile responses in the isolated aortic strips. These phenylephrine (10$^{-5}$ M)-induced contractile responses were depressed in the presence of high concentrations of bornyl acetate (10∼20 $\mu\textrm{g}$/ml), but not affected in low concentrations of bornyl acetate (2.5∼5$\mu\textrm{g}$/ml). High potassium (5.6 ${\times}$ 10$^{-2}$ M)-induced contractile responses were also greatly inhibited in the presence of bornyl acetate (2.5∼20 $\mu\textrm{g}$/ml) in a dose-dependent fashion. Bornyl acetate (1∼10 mg/kg) given into a femoral vein of the normotensive rat produced a dose-dependent depressor response, which is transient (data not shown). Interestingly, the infusion of a moderate dose of bornyl acetate (3mg/kg/30 min) made a significant reduction in pressor responses induced by intravenous norepinephrine. Collectively, these results obtained from the present study demonstrate that intravenous bornyl acetate causes a dose-dependent depressor action in the anesthetized rat at least partly through the blockade of adrenergic $\alpha$$_1$-receptors. bornyl acetate also causes vascular relaxation in the isolated aortic strips of the rat via the blockade of adrenergic $\alpha$$_1$-receptors, in addition to the unknown mechanism of direct vasorelaxation.

• The Korean Journal of Physiology
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• v.4 no.2
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• pp.83-89
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• 1970

전기적 자극법은 심맥관계기능의 신경성조절을 이해하기위해 널리 이용되는 방법이며, 일반적으로 중추신경에는 고빈도, 말초신경에서는 저빈도 자극에 의해 최대반응이 유발된다고 알려지고 있으며, 이는 흥분파의 민도가 말초로 내려오며 감소되기 때물이라 해석되고 있다. 또한편 신경계의 어떤 단위위에서건 자극민도가 어느 한계를 넘으면 유발된 반응은 유지되지를 못하고 감쇠소실되는 것으로 이는 주로 시납스간 흥분파전달능 부전에 기인될 것이라고 믿어지고있다. 그러나 고위주추계와 말초를 연결하고 있는 척수에 있어서는 아직 최적전기적 자극조건도 분명히 알려져 있지 않을 뿐 아니라 이 부위에서도 고빈도자극시에 반응이 어느 정도 감쇠하는지에 대한 보고가 없기에 이를 추구코자 저자는 고양이의 상부경수를 면수와 연결부에서 완전 절단하기 전후 여러가지 자극조건으로 자극하여 몇 가지 결론을 얻었기에 보고하는 바이다. 1) 연수와 연결부에서 완전절단을 하기 전에는 경수$(C_1{\sim}C_2)$의 백질, 회백질의 여러부위에서 심맥관반응이 유발되었으나 절단후에는 백질중의 만두부위(좌 $2{\sim}3\;mm$, 배면으로 부터 $0.3{\sim}1.0\;mm$및 $2.5{\sim}3.5\;mm$)에만 반응이 유발되었으며, 이 두 부위는 심맥관계기능을 지배조절하는 원심성 섬유의 통로라고 사료되었다. 2) 최대반응은 자극조건(빈도 자극파지속시간 강도) 100/sec-1 mesc-3V 및 20/sec-3 msec-3V에서. 최장지속반응은 20/sec-3msec에서 유발되었으므로, 후자가 척수부에 있어 심맥관계반응을 유발키 위한 최적자극조건으로 생각된다. 3) 자극면도 20/sec 이하에서 반응유지가 잘된다는 결과는 생리적 조건하에서 척수를 통과하는 흥분파의 빈도가 20/sec를 넘지 않을 것이란 것을 시사한다. 4) 반응지속정도는 최초의 최대반응의 반으로 감쇠되기까지 소요되는시간 즉 50% 반응감쇠시간으로 표시하였으며, 척수에서는 대뇌피질 및 간뇌에서보다 심맥관계반응의 50%반응감쇠시간이 현저히 긴 것을 알 수 있었다.

• Archives of Pharmacal Research
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• v.26 no.3
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• pp.214-223
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• 2003

The present study was conducted to investigate the effects of green tea extract (GTE) on arterial blood pressure and contractile responses of isolated aortic strips of the normotensive rats and to establish the mechanism of action. The phenylephrine ($10^{-6}~10^{-5}M$)-induced contractile responses were greatly inhibited in the presence of GTE (0.3~1.2 mg/mL) in a dose-dependent fashion. Also, high potassium ($3.5{\times}10^{-2}~5.6{\times}10^{-2}{\;}M$)-induced contractile responses were depressed in the presence of 0.6~1.2 mg/mL of GTE, but not affected in low concentration of GTE (0.3 mg/mL). However, epigallocatechin gallate (EGCG, $4~12{\;}{\mu}g/mL$) did not affect the contractile responses evoked by phenylephrine and high $K^+$. GTE (5~20 mg/kg) given into a femoral vein of the normotensive rat produced a dose-dependent depressor response, which is transient. Interestingly, the infusion of a moderate dose of GTE (10 mg/kg/30 min) made a significant reduction in pressor responses induced by intravenous norepinephrine. However, EGCG (1 mg/kg/30 min) did not affect them. Collectively, these results obtained from the present study demonstrate that intravenous GTE causes a dose-dependent depressor action in the anesthetized rat at least partly through the blockade of adrenergic $\alpha_1$-receptors. GTE also causes the relaxation in the isolated aortic strips of the rat via the blockade of adrenergic $\alpha_1$-receptors, in addition to the unknown direct mechanism. It seems that there is a big difference in the vascular effect between GTE and EGCG.

• Natural Product Sciences
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• v.20 no.3
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• pp.216-225
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• 2014

The present study was designed to investigate whether ethylacetate (EtOAc) fraction extracted from Rubus coreanum affect the contractility of the isolated thoracic aortic strips and blood pressure of normotensive rats. The EtOAc fraction ($400{\mu}g/mL$) significantly depressed both phenylephrine (PE, $10{\mu}M$)- and high $K^+$ (56 mM)-induced contractile responses of the isolated thoracic aortic strips in a concentration-dependent fashion. In the simultaneous presence of L-NAME (an inhibitor of NO synthase, $300{\mu}M$) and EtOAc ($400{\mu}g/mL$), both PE- and high $K^+$-induced contractile responses were recovered to the corresponding control level in comparison with inhibition of EtOAc-treatment alone. Moreover, in the simultaneous presence of EtOAc after pretreatment with 0.4% CHAPS, both PE- and high $K^+$-induced contractile responses were recovered to the corresponding control level compared to the inhibitory response of EtOAc-treatment alone. Also, in anesthetized rats, EtOAc fraction (0.3~3.0 mg/kg) injected into a femoral vein dose-dependently produced depressor responses. This hypotensive action of EtOAc fraction was greatly inhibited after treatment with phentolamine (1 mg/kg), chlorisondamine (1 mg/kg), L-NAME (3 mg/kg/30 min) or sodium nitroprusside ($30{\mu}g/kg/30 min$). Intravenous infusion of EtOAc fraction (1.0~10.0 mg/kg/30 min) markedly inhibited norepinehrine-induced pressor responses. Taken together, these results demostrate that EtOAc causes vascular relaxation in the isolated rat thoracic aortic strips as well as hypotensive action in anesthetized rats. These vasorelaxation and hypotension of EtOAc seem to be mediated at least by the increased NO production through the activation of NO synthase of vascular endothelium, and the inhibitory adrenergic modulation.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.10 no.11
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• pp.3473-3479
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• 2009

The pharmacological profile of KR-31081, a newly synthesized AT1 receptor antagonist, was evaluated in pithed rats, conscious renal hypertensive rats (RHRs) and conscious furosemide-treated beagle dogs. In pithed rats, KR-31081 (i.v.) induced a non-parallel right shift in the dose-pressor response curve to angiotensin II (ID50: 0.05 mg/kg) with a dose-dependent reduction in the maximum responses; this antagonistic effect was about 40 times more potent than losartan (ID50: 1.74 mg/kg) which showed competitive antagonism. KR-31081 did not alter the responses induced by other agonists such as norepinephrine and vasopressin. In RHRs, orally given KR-31081 produced a dose-dependent and long-lasting (>24 h) antihypertensive effect with a higher potency to losartan (ED20: 0.30 and 3.36 mg/kg, respectively). In furosemide-treated dogs, orally given KR-31081 produced a dose-dependent and long-lasting (>8h) antihypertensive effect with a rapid onset of action (time to Emax: 1-1.5 h) and 20-fold greater potency than losartan (ED20: 0.41 and 8.13 mg/kg, respectively). These results suggest that KR-31081 is a potent, orally active AT1 receptor antagonist useful for the research and diagnostic tools as an added exploratory potential.

• Journal of the East Asian Society of Dietary Life
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• v.9 no.3
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• pp.378-385
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• 1999

A reduced NaCl intake for the general population of the world has been recommended to reduce the overall blood pressure level and hence to reduce the overall incidence of cardiovascular disease. A high NaCl diet convincingly contributes to elevated arterial pressure in humans and animal models of hypertension. Among individuals there is considerable variability of blood pressure responsiveness to NaCl intake. In normotensive as well as hypertensive subjects, blood pressure can be judged to be salt sensitivity (SS) when observed to vary directly and substantially with the net intake of NaCl. The prevalence of SS in normotensive adults in the U.S. ranges from 15% to 42% and in hypertensive adults from 28% to 74%. SS is a risk factor for hypertension and may be an important marker in the identification of children for hypertension prevention programs. High NaCl intakes produce expansion of the extracellular fluid volume and thus increase blood pressure. Nonchloride salts of sodium does not expand the extracellular fluid volume and does not alter blood pressure. Blood pressure response to NaCl may be modified by other components of the diet. Low dietary intakes of potassium or calcium augment NaCl-induced increases of blood pressure. Conversely, high dietary intakes of potassium or calcium attenuate NaCl-induced hypertension. A greater intakes of potassium or calcium may prevent or delay the occurrence of hypertension. SS occurs when dietary potassium is even marginally deficient but is dose-dependently suppressed when dietary potassium is increased within its normal range. Orally administered KHCO$_3$, abundant in fruits and vegetates, but not KCl has a calcium-retaining effect which may contributed to its reversal of pressor effect of dietary NaCl. Since nutrients other than NaCl also affect blood pressure levels, a reduced NaCl intake should be only one component of a nutritional strategy to lower blood pressure.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.63-70
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• 1988

Alterations in splanchnic circulatory hemodynamics along with reactivities to the alpha adrenoceptor agonists were assessed in association with the preventive effects of propranolol 10 days after portal ligation. Decreases in precapillary resistance (Ra) and postcapillary resistance (Rv) along with increases in mesenteric blood flow (MBF) and capillary pressure (CP) were observed in conjunction with an increment of splenic pulp pressure (SPP). Dose-dependent increase in Rv in response to noradrenaline, increases in Ra and RV to adrenaline, and increases in superior mesenteric arterial pressure (SMAP), Ra and Rv to phenylephrine observed in sham group were significantly attenuated by portal vein stenosis. In PPL-3 group (propranolol 3 mg/kg, i.p. three times daily for 10 days), MBF was significantly decreased in association with decrease in mesenteric venous pressure (MVP) when compared with those of protal ligated (PL) group, and decreased Ra and Rv in PL group were recovered toward the values of sham group. Likewise, in PPL-1 group (propranolol 5 mg/kg, i.p. once daily for 10 days), the pressor response of Rv to adrenaline was recovered up to the level of sham group. Thus, it is suggested that decreases in Ra and Rv in association with increases in MBF and CP may have a close relevance to the increased SPP, and the changes in circulatory hemodynamics and vascular reactivities were effectively reversed by longterm propranolol treatment. Based on these results, it is concluded that these changes observed in portal hypertension are closely related with the altered functions of the adrenoceptors in the splanchnic vascular beds.

• The Korean Journal of Physiology
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• v.17 no.2
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• pp.93-101
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• 1983

A possibility whether the appearance of adaptation to cold climate during winter could occur or not in Taegu area was evaluated by comparing the data obtained in winter with that obtained by the same method in summer. Circulatory response was induced by the immersion of one hand in the cold water. The systemic and local responses in the blood circulation from the immersed hand and the unimmersed opposite hand were observed simultaneously. In addition Galvanic skin resistance(GSR) that is influenced by the activity of autonomic nervous system and the vascular tonicity was recorded. The experiment was performed by examining sixty healthy college students in winter and fifty in summer, whose mean age was 21.0, mean weight $60.6{\pm}0.90\;kg(male)$ and $48.3{\pm}0.98\;kg(female)$. The cold stimulus was applied by immersing the left hand into the cold water of $5^{\circ}C$ for 3 minutes, and the response was observed on immersed left hand and unimmersed right hand simultaneously. The observation was made through determining mean blood pressure, heart rate, amplitude of photoelectric capillary pulse (APCP) and GSR. The results obtained are as follows: The mean blood pressure was elevated during the cold stimulation. The increase of blood pressure in summer was more remarkable than in winter. At the recovery period the blood pressure was decreased to the control level in winter but the decrease below the control level was observed in summer. The increase of heart rate in summer was more remarkable than in winter during the cold stimulation. At the recovery period heart rate in both winter and summer was decreased below the control level. During the cold stimulation the APCP was decreased on both hands in winter. However it was more prominent on left hand indicating additional direct cold effect on immersed hand. In summer, the decrease of APCP during immersion was less remarkable than that in winter, but the regain of APCP was faster than that in winter at the recovery period. And the prompt increase of APCP over the control level has been obtained at the 3 minutes of the recovery period. The GSR was remarkably increased on immersed hand but slightly decreased on unimmersed opposite hand during the cold stimulation. Thus the finding on immersed hand indicates that the local direct effect of cold water is more prominent than the systemic effect, where as the finding on unimmersed hand indicates that the circulatory response to painful stress elicited by the cold stimulation is more prominent than cold temperature itself. In summary, it seems that the systemic circulatory response to the local cold stimulation of the one hand is arised more from the secondary elicited pain sensation and less from the low water temperature. On the contrary to the report of Kim et $al^{39)}$, the adaptation phenomena in blood pressure to the relatively mild cold climate in winter was not observed in this study. The difference of circulatory response observed in this study between winter and summer may be due to the difference of the magnitude of subjective sensation of the cold water stimulation by the seasonal changes in air temperature.

• The Korean Journal of Physiology
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• v.27 no.1
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• pp.57-66
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• 1993

Effects of a voltage dependent calcium channel antagonist, nifedipine, on the responses of blood pressure, and secretion of atrial natriuretic peptide (ANP) and aldosterone to angiotensin II (Ang II) were compared in male Wistar and spontaneously hypertensive rats (SHR). A low, control or high sodium diet (2, 10 or 25 mmol Na/100 g diet) was fed for 6 weeks from the age of 6 weeks. On the morning of the experiment catheters were inserted under ether anesthesia in the femoral artery for pressure recording and blood sampling, and in the femoral vein for drug infusion. Ang II was infused at a rate of 250 ng/kg/min for 20 min. Nifedipine mixed with Ang II was infused at a rate of $16{\mu}g/kg/min$ for 20 min. Arterial blood samples were collected before and after infusion of Ang II with or without nifedipine. The control plasma level of aldosterone was inversely related to the amount of salt intake, whereas the plasma ANP level was not different between the salt groups. SHR showed a higher basal plasma ANP but a lower aldosterone concentration than Wistar rats. Infusion of Ang II produced a significant increase in blood pressure and plasma levels of aldosterone and ANP: The % increase was not significantly different either between the salt groups or between SHR and Wistar rats. SHR showed a greater pressor response to Ang II but a remarkably smaller decrease in heart rate after Ang II infusion than Wistar rats, With increasing sodium intake, the effect of Ang II on aldosterone secretion was decreased, whereas that on ANP secretion or blood pressure was not changed. Nifedipine decreased the responses of blood pressure and heart rate to Ang II in all groups. Nifedipine caused almost a complete inhibition of Ang II induced ANP secretion, but only a partial inhibition of Ang II induced aldosterone secretion or vasoconstriction. These results indicate that calcium dependent processes were involved in Ang II induced vasoconstriction, and secretions of aldosterone and ANP. However, the calcium dependent process far ANP secretion was considerably different from that for aldosterone secretion or vasoconstriction evoked by ang II. The ang II induced increase in ANP secretion appeared to be caused primarily by activating voltage-dependent calcium channels, whereas Ang II induced aldosterone secretion and vasoconstriction was not.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.49-60
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• 1992

This study was designed to evaluate the responses of cardiovascular system to endothelin (ET) and neuropeptide Y (NPY) in 12 week-old SHR treated with or without enalapril (ENP) for 6 weeks. The diastolic blood pressure and heart rate were lower in ENP-treated SHR than in control. The pressor response to intravenous, but not intracerebroventricular, ET or NPY was attenuated by ENP treatment. The chronotropic action induced by electrical stimulation was attenuated by ENP or ET. The negative chronotropic action of ET was blocked by yohimbine. The increase in aortic tension induced by electrical field stimulation (EFS) was depressed in ENP-treated group as compared with non-treated group, and enhanced by ET, but not NPY, in the non-treated group. The ET-induced increase in tension was enhanced by removal of endothelium in the control group but not in ENP-treated group. The plasma concentration of norepinephrine and ET-induced increase in concentration of norepinephrine and epinephrine in plasma were decreased in ENP-treated group. These results suggest that preventive effect of enalapril on the development of hypertension may result from depressing vasoactive action of endothelin and neuropeptide Y, and sympathetic neurotransmission at peripheral nervous system.