Contractile Effect of Ultraviolet Light on Isolated Thoracic Aortae of Rats

백영홍,강성돈,강정채,Baik, Yung-Hong,Kang, Seong-Don,Kang, Jung-Chaee The Korean Society of Pharmacology 1993 대한약리학잡지 Vol.29 No.1

Ultraviolet light radiation (UVR) did not affect resting tension of isolated thoracic aortae of rats. In aortic rings contracted with phenylephrine, however, UVR produced contractile and relaxant responses in preparations with and without endothelium, respectively. The contractile response was dependent upon the duration $(10{\sim}320\;sec)$ of irradiation, while the relaxation was not. UVR-induced contractions in endothelium-intact rings were significantly potentiated by increasing the concentrations of phenylephrine from $10^{-7}M$ to $10^{-5}M$, and also by addition of $10^{-6}M$ acetylcholine, $10^{-7}M$ isoproterenol and $3.5{\times}10^{-8}M$ nitroglycerine. However, addition of $10^{-6}M$ phentolamine, or $10^{-7}M$ to $10^{-6}M$ LY83583 inhibited the contraction or reversed the contraction to a relaxation. In endothelium-removed preparations the UVR-induced relaxation was attenuated by increasing concentractions of phenylephrine, and by addition of isoproterenol, nitroglycerin, phentolamine or LY83583. These results suggest that UVR produces contractile and relaxant responses in rat thoracic aortae with and without endothelium, respectively, and that the contractile effect results from the inhibition of endothelium-derived relaxing factor (EDRF) release by UVR the inhibition of and/or is in part re-lated to some endothelium-derived contractile factors (EDCFs). 자외선조사는 흰쥐흉부대동맥의 휴지기장력에 거의 영향을 미치지 못했으나, phenylephrine으로 수축된 표본에서는 자외선조사로 내피세포가 존재하면 수축반응을, 내피세포가 제거되면 이완반응이 나타났다. 이 수축반응은 조사시간의 길이($10{\sim}320$초)에 비례하여 증가하였으나 이완반응은 그렇지 못하였다. 내피세포 존재표본에서 자외선의 수축반응은 phenylephrine농도의 증가($10^{-7}{\sim}10^{-5}M$) 그리고 $acetylcholine(10^{-6}M)$, $isoproterenol(10^{-7}M)$ 및 $nitroglycerin(3.5{\times}10^{-8} M)$의 추가투여시 크게 강화되었다. 그러나 $phentolamine(10^{-6}M)$ 또는 $LY83583(10^{-7},10^{-6}M)$의 추가투여시에는 자외선 수축반응이 억제 또는 이완반응으로 역전되었다. 내피세포 제거표본에서의 자외선 이완반응은 phenylephrine농도의 증가 그리고 isoproterenol, nitroglycerine, phentolamine 및 LY83583의 추가투여시 유의하게 감약되었다. 이상의 성적은 흰쥐 적출 흥부대동맥에서 자외선조사는 내피세포 존재유무에 따라 수축과 이완반응이 각각 나타나며, 수축반응은 자외선에 의한 EDRF 유리억제 또는 부분적으로 어떤 EDCF와도 관련이 있음을 시사하고 있다.

흰쥐 적출 흉부대동맥근의 자외선 수축반응에 관하여

백영홍(Yung Hong Baik),강성돈(Seong Don Kang),강정채(Jung Chaee Kang) 대한약리학회 1993 대한약리학잡지 Vol.29 No.1

자외선조사는 흰쥐흉부대동맥의 휴지기장력에 거의 영향을 미치지 못했으나, phenylephrine으로 수축된 표본에서는 자외선조사로 내피세포가 존재하면 수축반응을, 내피세포가 제거되면 이완반응이 나타났다. 이 수축반응은 조사시간의 길이(10 ~ 320초)에 비례하여 증가하였으나 이완반응은 그렇지 못하였다. 내피세포 존재표본에서 자외선의 수축반응은 phenylephrine농도의 증가(10^-7 ~ 10^-5M) 그리고 acetylcholine(10^-6M), isoproterenol(10^-7M) 및 nitroglycerin(3.5 × 10^-8 M)의 추가투여시 크게 강화되었다. 그러나 phentolamine(10^-6M) 또는 LY83583(10^-7,10^-6M)의 추가투여시에는 자외선 수축반응이 억제 또는 이완반응으로 역전되었다. 내피세포 제거표본에서의 자외선 이완반응은 phenylephrine농도의 증가 그리고 isoproterenol, nitroglycerine, phentolamine 및 LY83583의 추가투여시 유의하게 감약되었다. 이상의 성적은 흰쥐 적출 흥부대동맥에서 자외선조사는 내피세포 존재유무에 따라 수축과 이완반응이 각각 나타나며, 수축반응은 자외선에 의한 EDRF 유리억제 또는 부분적으로 어떤 EDCF와도 관련이 있음을 시사하고 있다. Ultraviolet light radiation (UVR) did not affect resting tension of isolated thoracic aortae of rats. In aortic rings contracted with phenylephrine, however, UVR produced contractile and relaxant responses in preparations with and without endothelium, respectively. The contractile response was dependent upon the duration (10 ~ 320 sec) of irradiation, while the relaxation was not. UVR-induced contractions in endothelium-intact rings were significantly potentiated by increasing the concentrations of phenylephrine from 10^-7M to 10^-5M, and also by addition of 10^-6M acetylcholine, 10^-7M isoproterenol and 3.5 × 10^-8M nitroglycerine. However, addition of 10^-6M phentolamine, or 10^-7M to 10^-6M LY83583 inhibited the contraction or reversed the contraction to a relaxation. In endothelium-removed preparations the UVR-induced relaxation was attenuated by increasing concentractions of phenylephrine, and by addition of isoproterenol, nitroglycerin, phentolamine or LY83583. These results suggest that UVR produces contractile and relaxant responses in rat thoracic aortae with and without endothelium, respectively, and that the contractile effect results from the inhibition of endothelium-derived relaxing factor (EDRF) release by UVR the inhibition of and/or is in part re-lated to some endothelium-derived contractile factors (EDCFs).

혈관평활근에 대한 Methylene Blue의 수축작용 - 가토흉부대동맥근과 돼지장간막동맥근 -

백영홍(Yung Hong Baik),최수용(Soo Yong Choi),김재하(Jae Ha Kim),조남기(Nam Kee Choi) 대한약리학회 1990 대한약리학잡지 Vol.26 No.1

가토흉부대동백근에서 MeB와 gentian violet는 용량-의존성 수축반응을 일으켰으나 evans blue와 eosine yellowish는 전혀 수축반응을 일으키지 못하였다. MeB는 돼지 장간막 동맥에서도 용량-의존성 수축반응을 일으켰다. 양표본에서 MeB 10^-4 M의 단회투여는 수축반응에 이어 이완반응이 나타나는 양상성 반응을 일으켰으나, tyramine은 지속적인 수축반응을 일으켰다. Tyramine의 수축반응은 반복적이었으나 MeB의 그것은 일차 수축반응 후 3 ~ 5시간 후까지도 반복되지 않았다. Tyramine 10^-4 M의 최대 수축반응 상태에서 MeB 10^-4 M의 추가투여는 현저한 추가수축반응을 일으켰으나 반대로 MeB의 최대수축반응 상태에서 tyramine의 추가투여는 그이상의 수축반응을 일으키지 못하였다. Tyramine과 MeB 수축반응은 교감신경계 악물로 소실 또는 유의하게 억제되었다. Tyramine 수축반응은 MeB 수축보다 guanethidine과 6-hydroxydopamine에 더 예민한 반면, Ca²⁺-free PSS와 reserpine에 대하여는 MeB 수축반응이 tyramine 수축보다 더 예민하였고 prazosin하에서는 두 수축반응이 비슷하게 억제되었다. MeB 수축반응은 6-hydroxydopamine으로 유의하게 억제는 되었으나 소실되지 않았고, MeB 수축반응 관찰후에는 tyramine 뿐만아니라 6-hydroxydopamine의 수축반응도 소실되었다. 이상의 성적은 가토흉부대동맥과 돼지 장간막동맥에서 MeB 수축반응은 부분적으로 세포외 calcium 의존성이고 adrenaline성 신경발단으로부터의 norepinephrine유리에 기인하며, MeB의 norepinephrine유리 및 고갈작용이 tyramine 또는 6-hydroxydopamine의 작용보다 더 강력함을 시사하고 있다. Methylene Blue (MeB) and gentian violet (10^-6 ~ 10^-4 M) produced contractions in isolated thoracic aortic preparations of rabbits in a dose-dependent fashion, while other dyes, evans blue and eosine yellowish, did not affect the basal tension in the same range of doses. Porcine mesenteric arterial rings also responded to MeB with dose-dependent contractions. Single dose of 10^-4 M MeB produced a biphasic response: contraction followed by relaxation. The contraction developed slowly within 2 ~ 4 min and peaked in about 20 minutes and then slowly relaxed to the basal level. Tyramine (10^-4 M) also induced contraction but it developed faster and was more persistent than that of MeB. While the tyramine-induced tension was reproducible, the MeB-induced one wat not reiterable until 3 to 5 hours after washing out the MeB. Adding 10^-4 M MeB further potentiated the contraction induced by 10^-4 M tyramine. However, the MeB contraction was not affected by further addition or tyramine. Both tyramine- and MeB-induced tensions were abolished or significantly inhibited by pretreatment with various drugs acting on the sympathetic nervous system. The tyramine-induced tension was more sensitive to guanethidine and 6-hydroxydopamine than the MeB-induced tension, while the latter was more sensitive to Ca²⁺-free PSS and reserpine. But they have similar sensitivity to prazosin. The MeB-induced tension was significantly inhibited but not abolished by 6-hydroxydopamine pretreatment. However, either tyramine or 6-hydroxydopamine could not affect the basal tension of the ring that MeB once had been tested. These results suggest that MeB-induced contractions of rabbit thoracic aorta and porcine mesenteric artery result from a release of endogenous norepinephrine from adrenergic nerve endings and are dependent in part on extracellular calcium, and that the potency of MeB to release or to deplete norepinephrine is greater than that of either tyramine or 6-hydroxydopamine.

Modification of Endothelium on Contractile Response of Brain Vessels to Contracting Agents

국영종,백영홍,김종근,최봉규,최수형,김연인,Kook, Young-Johng,Baik, Yung-Hong,Kim, Jong-Keun,Choi, Bong-Kyu,Choi, Soo-Hyung,Kim, Yung-In The Korean Society of Pharmacology 1988 대한약리학잡지 Vol.24 No.2

돼지, 가표 및 가토의 뇌동맥에서 기저동맥 (basilar artery, BA)과 circle of willis동맥 (WC)의 동맥환을 만들어 혈관수축제와 calcium 길항제의 효과 그리고 내피세포의 역할은 검토하였다. 돼지 BA와 WC에 서 norepinephrine (NE), phenylephrine (PE)및 epinephrine (EP)은 propranolol $10^{-6}M$ 전처리하에서 그리고 KCI, histamine, 5-hydroxytryptamine (5-HT) 및 angiotensin은 모두 용량의존성 수축반응을 일으켰다. 그 최대수축력은 angiotensin에서 가장 적었고, 5-HT에서 가장 강력하였다. KCI 35 mM수축반응은 calcium 길항제로 용량의존성으로 억제되었고, 그 효력은 nifedipine > > diltiazem > flunarizine > oxybutynin > isosorbide dinitrate (ISDN) > glycerl trinitrate의 순서였다. 5-HT $10^{-5}M$의 수축반응은 nifedipine으로는 용량의존성으로 억제 되었으나 diltiazem과 ISDN으로는 경미한 억제만을 일으켰다. 내피세포동맥환에서 KCI 35 mM의 수축반응은 acetylcholine (ACh)으로 거의 영향받지 않았으나 $PGF_{2{\alpha}}\;10^{-5}M$의 수축반응은 ACh과 adenosine으로 용량의존성으로 억제되었고, 이 내피세포 의존성억제는 nifedipine $10^{-6}M$로는 영향받지 않으나 methylene blue $50\;{\mu}M$로는 현저히 억제되었다. 네피제거동맥환에의 $PGF_{2{\alpha}}$의 수축반응은 ACh의 영향이 없거나 더욱 수축되었다. 내피세포를 제거하지 않은 가토흉부대동맥편을 bath에 함께 넣어주면 ACh의 용량의존성 이완반응이 나타났고 이 이완반응도methylene blue로 억제되었다. 가묘 BA와 WC에서 5-HT와 NE는 용량의존성 수축반응을 일으켰고 ACh도 내피세포 존재유무와 관계없이 강력한 용량의존성 수축반응을 일으켰으며 그 최대수축력은 ACh에서 가장 강력하였다. 내피세포동맥환에서 5-HT $10^{-5}M$의 수축반응은 ACh에 의하여 이완반응없이 더욱 수측되었다. 가토 BA에서 5-HT와 NE는 응량의존성 수축반응을 일으졌고5-HT의 수축반응이 더욱 현저하였다. 내피세포동맥환에서 5-HT $10^{-5}M$의 수축반응은 ACh $10^{-5}M$로 현저하게 이완되있고 이 내피세포의존성 이완반응은 atropine $10^{-7}M$로는 억제되었으나 diltiazem $10^{-6}M$로는 거의 억제되지 않았다. 이상의 실험성적은 돼지와 가토의 뇌동맥에서 ACh은 내피세포-의존성 이완반응을 일으키며그 이완반응은 muscarinic receptor를 통해 나타났고, 가묘뇌동맥에서 ACh은 혈관수축제의 역할을 갖고 있음을 시사하고 있다. To delineate the mechanisms of vasoconstriction and vasodilation in cerebral arteries the effects of some vasoconstrictors and calcium antagonists on the basilar artery (BA) and arterial circle of Willis (WC) were examined and also the role of endothelium in the action of these drugs was investigated in pigs, cats and rabbits. In pig cerebral arteries, dose-dependent contractile responses were elicited by KCI, histamine, 5-hydroxytryptamine (5-HT) and angiotensin, but norepinephrine (NE), phenylephrine (PE) and epinephrine (EP) elicited dose-dependent contractions only under pretreatment with propranolol 10-6 M. The magnitudes of maximal contractile effects of these drugs were different from each other, and 5-H~ was the largest and angiotensin the smallest. Some calcium antagonists dose-dependently inhibited KCI (35 mM)-induced contraction and the order of potency in inhibiting the contraction was nifedipine > > diltiazem > flunarizine > oxybutynin > isosorbide dinitrate (ISDN) > glyceryl trinitrate. 5-HT (10-6 M)-induced contraction was dosedependently inhibited by nifedipine but slightly inhibited by diltiazem and ISDN. In rings with intact endothelium, KCI (35 mM)-induced contraction was not affected by acetylcholine (ACh) but $PGF_{2{\alpha}}$ (lO-SM)-induced contraction was dose-dependently relaxed by ACh and adenosine. This endothelium-dependent relaxation was not affected by nifedipine (l0-6M)-pretreatment but markedly inhibited by methylene blue (50,uM)-pretreatment. In the porcine arterial rings without endothelium, ACh had no effect or even contracted the $PGF_{2{\alpha}}-induced$ contraction. However, the dosedependent relaxing effect of ACh appeared when the deendothelized porcine ring and rabbit thoracic aorta with intact endotheli urn were simultaneously suspended into a bath and this relaxing effect was also inhibited by methylene blue-pretreatment. In cat cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and ACh also produced dose-dependent contraction regardless of the existence of endothelium. ACh-induced contraction was most prominent. 5-HT (IO-SM)induced contraction was not relaxed but contracted additionally by ACh even in the intact endothelial ring. In rabbit cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and 5-HT-induced contraction was more prominent. In the intact endothelial preparations, 5-HT (lO-s M)-induced contraction was markedly relaxed by the addition of ACh( IO-SM) and this endothelium-dependent relaxing effect was inhibited by atropine (l0-7M)-pretreatment but notaffected by diltiazem (l0-6M)-pretreatment. These results suggest that ACh elicits endotheliumdependent relaxing effect mediated by muscarinic receptors in cerebral arteries of pig and rabbit, and that ACh acts as vasoconstrictor in cat cerebral artery.

Study on Relaxing Effect of Oxybutynin on the Contractile Response of Arterial Smooth Muscle

고재기,백영홍,Ko, Jae-Ki,Baik, Yung-Hong The Korean Society of Pharmacology 1988 대한약리학잡지 Vol.24 No.1

돼지 우관상동백을 적출하여 항경련제인 oxybutynin의 약리작용을 조사하였다. 1. Acetylcholine (ACh)과 KCl은 관상동맥을 수축시켰고 이 수축효과는 용량의존적이었다. ACh의 수축효과는 내피손상표본 $(EC_{50}=0.52\;{\mu}M)$에서 내피표본 $(EC_{50}=0.52\;{\mu}M)$보다 약 2배 강화되있으나 KCl의 수축효과는 양군간에 차이가 없었다. 2. $ACh(1.0\;{\mu}M)$의 수축효과는 oxybutynin과 atropine에 의 하여 용량의존적으로 억제되었고 두 약물의 $(IC_{50}$는 각각 11.0 nM과 0.47 nM로 atropine이 약 23배나 더 예민하였다. 그러나 KCl (35 mM)의 수축효과는 atropine으로는 전혀 영향받지 않았고 oxybutynin으로는 용량의존적으로 억제 되었으며 $(IC_{50}=49.7\;{\mu}M)$이였다. 3. ACh의 용량반응곡선은 oxybutynin $(IC_{50}=11\;nM)$ 및 atropine $(IC_{50}=0.47\;nM)$ 전처 리 하에서 우측으로 평 행 이 동되 있고, KCI의 용량반응곡선은 oxybutynin $(IC_{50}=49.7\;nM)$ 전처리하에서 우측으로 비상경적 이동을 일으켰다. 4. Oxybutynin은 Bay K 8644 $(0.1\;{\mu}M)$의 수축효과를 용량의존적 으로 억제하였고 $(IC_{50}=63.0\;{\mu}M)$이었으며 , histamine $(35\;{\mu}M)$의 수축효과는 oxybutynin의 최대량 $(500\;{\mu}M)$으로 부분억제 (최대 50%)만을 일으켰다. 이상의 성적으로 적출돼지 관상동백에서 내피세포는 ACh에 의한 수축반응에 억제적 영향을 미치며, oxybutynin은 강력한 muscarine receptor 차단작용과 calcium influx 억제작용에 의하여 혈관근 이완을 일으킨다고 추론하였다. Pharmacological actions of an antispasmodic agent, oxybutynin were investigated in the isolated procine coronary arteries. The coronary rings were contracted by acetylcholine (ACh) and KCl in a dose-dependent fashion. The ACh-induced contractions were signifcantly potentiated by removal of endothelium and $EC_{50}=0.52\;{\mu}M$ of intact endothelial rings was about 2 times greater than $EC_{50}=0.28\;{\mu}M$ of rings without the endothelium. These results suggest that the endothelium plays an inhibitory role in ACh-induced contraction. Oxybutynin and atropine inhibited dose-dependently $1.0\;{\mu}M$ ACh-induced contraction and atropine inhibited dose-dependently $1.0\;{\mu}M$ ACh-induced contraction and the $IC_{50s}$ were 11.0 nM and 0.47 nM, respectively. Atropine did not affect 35 mM KCl-induced contraction but oxybutynin inhibited the contraction to the basal tension in a dose-dependent manner. The $IC_{50}$ of oxybutynin on the KCl-induced contraction was $49.7\;{\mu}M$. The dose-response curve to ACh was parallelly shifted to the right by pretreating coronary rings with $IC_{50}$ of atropine (0.47 nM) or oxybutynin (11.0 nM) but the curve to KC1 was rightward shifted in a noncompetitive manner under pretreatment with $IC_{50}$ of oxybutynin $(49.7\;{\mu}M$). Oxybutynin inhibited $0.1\;{\mu}M$ Bay K 8644-induced contraction to the basal tension in a dose dependent manner, but $35\;{\mu}M$ histamine-induced contraction was inhibited to only 50e/e of the original level even in maximal concentration $(5{\times}10^{-4}M)$ of oxybutynin. These results suggest that oxybutynin causes antispasmodic action through sensitive blocking action on muscarinic receptors and inhibitory action on calcium influx in the procine coronary artery.

Effects of Intracerebroventricular Calcium Antagonists on Changes of Blood Pressure and Heart Rate by Methoxamine and Clonidine in Rabbits

김종근,백영홍,Kim, Jong-Keun,Baik, Yung-Hong The Korean Society of Pharmacology 1986 대한약리학잡지 Vol.22 No.2

Urethane 마취 가토에서 뇌내 alpha-1및 alpha-2 adrenoceptor의 작용에 미치는 calcium antagonist의 영항을 알아보고자 뇌실내 methoxamine과 clonidine의 혈압및 심박수 변동에 미치는 diltiazem, nifedipine의 영향을 조사한 결과, 1). 뇌실내 methgramine(1mg)은 혈압상승및 심박수 감소를 일으켰고, 뇌실내 clonidine$(30{\mu}g)$은 혈압하강및 심박수 감소를 일으켰다. 2). 뇌실내 diltiazem과 nifedipine은 dose-dependent한 혈압하강을 일으켰으며 심박수 감소를 일으켰다. Diltiazem에 비하여 nifedipine은 혈압하강 효과는 크고 심박수 감소효과는 작았다. 뇌실내 diltiazem$(400{\mu}g)$, nifedipine$(35{\mu}g)$의 혈압하강 작용은 완만하고 지속적이었으나 같은 양의 정맥내 투여효과는 일과성이었다. 3). 뇌실내 diltiazem$(400{\mu}g)$이나 nifedipine$(35,\;350{\mu}g)$ 처리 후에 methoxamine(1mg)의 혈압상승 효과는 영향받지 않았으나 심박수감소 효과는 유의하게 감약되었다. 4). Clonidine의 혈압하강 작용은 뇌실내 diltiazem$(400{\mu}g)$이나 nifedipine$(35,\;350{\mu}g)$ 처리 후에 감약되었으나 정맥 내 diltiazem$(200{\mu}g/kg)$이나 nifedipine$(30{\mu}g/kg)$ 후에는 영향받지 않았다. Clonidine의 심박수 감소작용은 .뇌실내및 정맥내 diltiazem이나 nifedipine 처리후에 감약되었다. 5). 뇌실내 clonidine$(30{\mu}g)$ 처 리후 뇌실내 diltiazem$(400{\mu}g)$과 nifedipine$(350{\mu}g)$의 혈압하강및 심박수 감소효과는 영향 받지 않고 그대로 나타났다. 이상의 결과로 diltiazem과 nifedipine은 가토뇌내에서 methoxamine에 의한 혈압상승의 작용점인 alrfia-1 adrenoceptor의 흥분에는 영향을 미치지 못하나 clonidine의 작용점인 alpha-2 adrenoceptor의 흥분에 의한 혈압하강및 심박수 감소효과는 억제한다고 추론하였다. To delineate the relationship between subtypes of central alpha-adrenoceptor and central calcium channel, influences of intracerebroventricular (icv) diltiazem and nifedipine on the changes of blood pressure and heart rate by icv methoxamine and clonidine were investigated in urethane-anesthetized rabbits. 1) Methoxamine (1mg, icv) produced pressor and bradycardiac effect and clonidine $(30\;{\mu}g,\;icv)$ produced hypotension and bradycardia. 2) Icv diltiazem and nifedipine elicited dose-dependent deprcssor and bradycardiac responses. The depressor response to nifedipine was more prominent than that to diltiazem but the bradycardiac effect of nifedipine was smaller than that of diltiazem. The depressor responses to icy nifedipine $(35{\mu}g)$ and icv diltiazem $(400{\mu}g)$ were persistent but those to intravenous (iv) nifedipine $(35{\mu}g/kg)$ and diltiazem $(200{\mu}g/kg)$ were transient. 3) The pressor response to methoxamine was little affected by pretreatment with in diltiazem $(400{\mu}g)$ or icv nifedipine $(35,\;350{\mu}g)$ but the bradycardiac response to methoxamine was significantly attenuated by the same pretreatment. 4) The depressor response to clonidine was markedly attenuated by pretreatment with icv diltiazem $(400{\mu}g)$ or icv nifedipine $(35,\;350{\mu}g)$ but not affected by pretreatment with iv diltiazem $(200{\mu}g/kg)$ or iv nifedipine $(20{\mu}g/kg)$. Pretreatment with icv and iv diltiazem or nifedipine reduced the bradycardiac effect of clonidine. 5) Pretreatment with icv clonidine had no effect on the depressor and bradycardiac responses to in diltiazcm or icv nifedipine. These results indicate that diltiazem and nifedipine have no effect on icv methoxamine-induced pressor response elicited by the activation of central alpha-l adrenoceptors whereas the icv clonidine-induccd depressor and bradycardiac effects which result from the activation of central alpha-2 adrenoceptors are inhibited by the calcium antagonists.

동맥근 수축에 대학 Oxybutynin의 이완효과에 관한 연구

고재기(Jae Ki Ko),백영홍(Yung Hong Baik) 대한약리학회 1988 대한약리학잡지 Vol.24 No.1

돼지 우관상동백을 적출하여 항경련제인 oxybutynin의 약리작용을 조사하였다. 1. Acetylcholine (ACh)과 KCl은 관상동맥을 수축시켰고 이 수축효과는 용량의존적이었다. ACh의 수축효과는 내피손상표본 (EC₅₀=0.52μM)에서 내피표본 (EC₅₀=0.52μM)보다 약 2배 강화되있으나 KCl의 수축효과는 양군간에 차이가 없었다. 2. ACh(1.0μM)의 수축효과는 oxybutynin과 atropine에 의 하여 용량의존적으로 억제되었고 두 약물의 (IC₅₀는 각각 11.0 nM과 0.47 nM로 atropine이 약 23배나 더 예민하였다. 그러나 KCl (35 mM)의 수축효과는 atropine으로는 전혀 영향받지 않았고 oxybutynin으로는 용량의존적으로 억제 되었으며 (IC₅₀=49.7μM)이였다. 3. ACh의 용량반응곡선은 oxybutynin (IC₅₀=11 nM) 및 atropine (IC₅₀=0.47 nM) 전처 리 하에서 우측으로 평 행 이 동되 있고, KCI의 용량반응곡선은 oxybutynin (IC₅₀=49.7 nM) 전처리하에서 우측으로 비상경적 이동을 일으켰다. 4. Oxybutynin은 Bay K 8644 (0.1μM)의 수축효과를 용량의존적 으로 억제하였고 (IC₅₀=63.0μM)이었으며 , histamine (35μM)의 수축효과는 oxybutynin의 최대량 (500μM)으로 부분억제 (최대 50%)만을 일으켰다. 이상의 성적으로 적출돼지 관상동백에서 내피세포는 ACh에 의한 수축반응에 억제적 영향을 미치며, oxybutynin은 강력한 muscarine receptor 차단작용과 calcium influx 억제작용에 의하여 혈관근 이완을 일으킨다고 추론하였다. Pharmacological actions of an antispasmodic agent, oxybutynin were investigated in the isolated procine coronary arteries. The coronary rings were contracted by acetylcholine (ACh) and KCl in a dose-dependent fashion. The ACh-induced contractions were signifcantly potentiated by removal of endothelium and EC₅₀=0.52μM of intact endothelial rings was about 2 times greater than EC₅₀=0.28μM of rings without the endothelium. These results suggest that the endothelium plays an inhibitory role in ACh-induced contraction. Oxybutynin and atropine inhibited dose-dependently 1.0μM ACh-induced contraction and atropine inhibited dose-dependently 1.0μM ACh-induced contraction and the IC_50s were 11.0 nM and 0.47 nM, respectively. Atropine did not affect 35 mM KCl-induced contraction but oxybutynin inhibited the contraction to the basal tension in a dose-dependent manner. The IC₅₀ of oxybutynin on the KCl-induced contraction was 49.7μM. The dose-response curve to ACh was parallelly shifted to the right by pretreating coronary rings with IC₅₀ of atropine (0.47 nM) or oxybutynin (11.0 nM) but the curve to KC1 was rightward shifted in a noncompetitive manner under pretreatment with IC₅₀ of oxybutynin (49.7μM). Oxybutynin inhibited 0.1μM Bay K 8644-induced contraction to the basal tension in a dose dependent manner, but 35μM histamine-induced contraction was inhibited to only 50e/e of the original level even in maximal concentration (5 × 10^-4M) of oxybutynin. These results suggest that oxybutynin causes antispasmodic action through sensitive blocking action on muscarinic receptors and inhibitory action on calcium influx in the procine coronary artery.

가토에서 뇌실내 Calcium Antagonists가 Methoxamine과 Clonidine의 혈압및 심박수 변동에 미치는 영향

김종근(Jong Keun Kim),백영홍(Yung Hong Baik) 대한약리학회 1986 대한약리학잡지 Vol.22 No.2

Urethane 마취 가토에서 뇌내 alpha-1및 alpha-2 adrenoceptor의 작용에 미치는 calcium antagonist의 영항을 알아보고자 뇌실내 methoxamine과 clonidine의 혈압및 심박수 변동에 미치는 diltiazem, nifedipine의 영향을 조사한 결과, 1). 뇌실내 methgramine(1mg)은 혈압상승및 심박수 감소를 일으켰고, 뇌실내 clonidine(30μg)은 혈압하강및 심박수 감소를 일으켰다. 2). 뇌실내 diltiazem과 nifedipine은 dose-dependent한 혈압하강을 일으켰으며 심박수 감소를 일으켰다. Diltiazem에 비하여 nifedipine은 혈압하강 효과는 크고 심박수 감소효과는 작았다. 뇌실내 diltiazem(400μg), nifedipine(35μg)의 혈압하강 작용은 완만하고 지속적이었으나 같은 양의 정맥내 투여효과는 일과성이었다. 3). 뇌실내 diltiazem(400μg)이나 nifedipine(35, 350μg) 처리 후에 methoxamine(1mg)의 혈압상승 효과는 영향받지 않았으나 심박수감소 효과는 유의하게 감약되었다. 4). Clonidine의 혈압하강 작용은 뇌실내 diltiazem(400μg)이나 nifedipine(35, 350μg) 처리 후에 감약되었으나 정맥 내 diltiazem(200μg/kg)이나 nifedipine(30μg/kg) 후에는 영향받지 않았다. Clonidine의 심박수 감소작용은 .뇌실내및 정맥내 diltiazem이나 nifedipine 처리후에 감약되었다. 5). 뇌실내 clonidine(30μg) 처 리후 뇌실내 diltiazem(400μg)과 nifedipine(350μg)의 혈압하강및 심박수 감소효과는 영향 받지 않고 그대로 나타났다. 이상의 결과로 diltiazem과 nifedipine은 가토뇌내에서 methoxamine에 의한 혈압상승의 작용점인 alrfia-1 adrenoceptor의 흥분에는 영향을 미치지 못하나 clonidine의 작용점인 alpha-2 adrenoceptor의 흥분에 의한 혈압하강및 심박수 감소효과는 억제한다고 추론하였다. To delineate the relationship between subtypes of central alpha-adrenoceptor and central calcium channel, influences of intracerebroventricular (icv) diltiazem and nifedipine on the changes of blood pressure and heart rate by icv methoxamine and clonidine were investigated in urethane-anesthetized rabbits. 1) Methoxamine (1mg, icv) produced pressor and bradycardiac effect and clonidine (30μg, icv) produced hypotension and bradycardia. 2) Icv diltiazem and nifedipine elicited dose-dependent deprcssor and bradycardiac responses. The depressor response to nifedipine was more prominent than that to diltiazem but the bradycardiac effect of nifedipine was smaller than that of diltiazem. The depressor responses to icy nifedipine (35μg) and icv diltiazem (400μg) were persistent but those to intravenous (iv) nifedipine (35μg/kg) and diltiazem (200μg/kg) were transient. 3) The pressor response to methoxamine was little affected by pretreatment with in diltiazem (400μg) or icv nifedipine (35, 350μg) but the bradycardiac response to methoxamine was significantly attenuated by the same pretreatment. 4) The depressor response to clonidine was markedly attenuated by pretreatment with icv diltiazem (400μg) or icv nifedipine (35, 350μg) but not affected by pretreatment with iv diltiazem (200μg/kg) or iv nifedipine (20μg/kg). Pretreatment with icv and iv diltiazem or nifedipine reduced the bradycardiac effect of clonidine. 5) Pretreatment with icv clonidine had no effect on the depressor and bradycardiac responses to in diltiazcm or icv nifedipine. These results indicate that diltiazem and nifedipine have no effect on icv methoxamine-induced pressor response elicited by the activation of central alpha-l adrenoceptors whereas the icv clonidine-induccd depressor and bradycardiac effects which result from the activation of central alpha-2 adrenoceptors are inhibited by the calcium antagonists.

뇌척수액내 Na⁺ 농도 증가에 의한 심혈관 반응과 Amiloride 민감성 Na⁺ Channel과의 관계

국현(Hyun Kook),김재하(Jae Ha Kim),백영홍(Yung Hong Baik) 대한약리학회 1994 대한약리학잡지 Vol.30 No.3

Na⁺ 이동에 관여하는 약물을 가토 측뇌실내로 투여하여 나타난 반응을 관찰함으로써 심혈관 조절 중추의 Na⁺ channel과 뇌척수액내 Na⁺ 농도의 상승에 의한 심혈관 반응과의 관계를 밝히고자 하였다. 1 M NaCl 200μl을 urethane으로 마취된 가토의 측내실내로 투여시 승압과 서맥이 나타났고 이 서맥은 미주신경 절단으로 빈맥으로 역전되었다. Na⁺ 이동억제제인 amiloride의 뇌실내 투여는 승압 및 서맥을 일으켰고 미주신경 절단으로 영향을 받지 않았으며 NaCl주입에 의한 심혈관계 반응에 영향을 미치지 않았다. Amiloride 유도체인 benzamil은 그 자체로도 심혈관계 반응에 아무런 영향을 미치지 않았을 뿐 아니라 NaCl의 효과에도 영향을 주지 않았다. 미주신경 절단 가토에서 amiloride는 NaCl에 의한 빈맥을 서맥으로 역전시켰으나, 그 서맥의 정도는 NaCl의 전처치로 영향받지 않았다. 이상의 성적으로 amiloiride와 benzamil이 심혈관계에 미치는 영향은 각기 다르나 그들 모두 NaCl에 의한 심혈관계 반응에는 아무런 영향을 미치지 않음을 알았다. 이로부터 심혈관 조절 중추내 amiloride나 benzamil에 민감한 Na⁺ channel은 NaCl-유발 반응과는 관련이 없을 것이라 추론하였다. This study was undertaken to investigate the relationship between the Na⁺ channels of the cardiovascular regulation center and the responses to increased Na⁺ concentration in the cerebrospinal fluid (CSF), by observing the effects of icv administration of the agents affecting Na⁺ transport. Icv infusion of200μl of 1 M NaCl produced hypertension and bradycardia in the urethane-anesthetized rabbit, and the bradycardia was inhibited and reversed to tachycardia by vagotomy. Amiloride, a Na⁺ transport inhibitor, produced hypertension and bradycardia, which were not altered by vagotomy, and it did not affect the NaCl-induced responses. Benzamil, a derivative of amiloride with higher specificity, neither produced any cardiovascular effects by itself, nor affected the NaCl-induced responses. In vagotomized rabbits, icv amiloride reversed the NaCl-induced tachycardia to a bradycardia, but the bradycardiac effect was not altered by pretreating with NaCl. This study showed that although amiloride and benzamil slightly differ in their cardiovascular action, neither of them did affect the NaCl-induced responses. We suggest that the Na⁺ channels which are sensitive to amiloride or benzamil in the cardiovascular regulation center are not involved in the NaCl-induced response.

흰쥐 적출대동맥의 자외선 유발 기계적 반응시 cAMP 및 cGMP의 농도변화

류봉수,안호범,김대영,이삼용,조백현,백영홍 大韓成形外科學會 1994 Archives of Plastic Surgery Vol.21 No.4

When the isolated thoracic aortae of rats were contracted with 1 or 10 μM phenylephrine (PE), ultraviolet(UV) light irradiaion produced the contractile and relaxant and relaxant responses in preparations with and without endothelium, respectively, 1μM ACh relaxed PE-induced contraction in the intact endothelial preparation, but did not in the denuded one. On the other hand, nitroprusside (NP) and isoproterenol(ISP) produced relaxing resposes irrespective of the presence of the endothelium. In the Endothelium - intact preparation, ACh potentiated the UV light-induced contraction, but ISP did not. Both agents did not affect the UV light-induced relaxation in the denuded preparation. The cGMP level in tissue was decreased by removal of the endothelium, but the cAMP level was not. In both preparations with and without the endothelium combined treatment with NP 1μM after PE 10μM markeldly increased the cGMP level. However, combined treatment with PE 10μM + ACh 1μM increased cGMP level in the intact preparation only, and UV light irradiation for 3 min reduced the increment. Single treatment with PE 10μM and combined treatment with PE+ISP for 5min or PX+UV irradiation did not affect the cGMP level. And cAMP level of the intact endothelial preparation was increased in combined treatment with PE 10μM+ISP 1μM but not altered in any of the other conditions. These resluts suggest followings : ① UV light produces contraction of the rat thoracic aorta in endothelium-dependent fashoion, ② cAMP is not a factor to this response, ③ the UV light-induced relaxation is not related to the cGMP and the cAMP level in the tissue.