• Korean Journal of Veterinary Research
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• v.27 no.1
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• pp.35-40
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• 1987

Higenamine, a benzyltetrahydroisopuinoline analog isolated from aconite tuber, has potent isotropic action. Recent studies suggest it may have beta receptor agonistic property in that its inotropic action is blocked by propranolol in isolated rabbit heart. However, no study has been carried out on other organs than heart. Higenamine is expected to have pharmacological actions on smooth muscle on the ground that it has catecholamine moiety and tetrahydrosioquinoline nucleus in its chemical structure, both of which are well known to have smooth muscle relaxation effects. Therefore present study was aimed at determining whether higenamine has bronchodilating effect in isolated guinea pig trachea smooth muscle rich in adrenergic beta receptor and if any, it has agonistic effect on beta receptor. The results were summarized as follows : 1. Higenamine had remarkable bronchodilating effect in guinea pig tracheal smooth muscle in a dose-dependent manner. 2. Bronchodilator effect of higenamine in isolated guinea pig tracheal smooth muscle was blocked competitively by propranolol. The $pD_2$ value of higenamine in isolated guinea pig tracheal smooth muscle was 5.65 and the $pA_2$ value of propranolol against higenamine in the same preparation was 7.97.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.5
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• pp.297-303
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• 2012

This study was designed to elucidate high $K^+$-induced relaxation in the human gastric fundus. Circular smooth muscle from the human gastric fundus greater curvature showed stretch-dependent high $K^+$ (50 mM)-induced contractions. However, longitudinal smooth muscle produced stretch-dependent high $K^+$-induced relaxation. We investigated several relaxation mechanisms to understand the reason for the discrepancy. Protein kinase inhibitors such as KT 5823 (1 ${\mu}M$) and KT 5720 (1 ${\mu}M$) which block protein kinases (PKG and PKA) had no effect on high $K^+$-induced relaxation. $K^+$ channel blockers except 4-aminopyridine (4-AP), a voltage-dependent $K^+$ channel ($K_V$) blocker, did not affect high $K^+$ -induced relaxation. However, N(G)-nitro-L-arginine and 1H-(1,2,4)oxadiazolo (4,3-A)quinoxalin-1-one, an inhibitors of soluble guanylate cyclase (sGC) and 4-AP inhibited relaxation and reversed relaxation to contraction. High $K^+$-induced relaxation of the human gastric fundus was observed only in the longitudinal muscles from the greater curvature. These data suggest that the longitudinal muscle of the human gastric fundus greater curvature produced high $K^+$-induced relaxation that was activated by the nitric oxide/sGC pathway through a $K_V$ channel-dependent mechanism.

• The Korean Journal of Physiology
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• v.27 no.2
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• pp.199-207
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• 1993

To study the underlying mechanism through which the endothelium-dependent relaxation is inhibited by blocking the $Na^+\;-K^+$ pump, the effects of $Na^+\;-K^+$ pump blockade on the release of EDRF and its relaxing activity were examined, using organ bath study, bioassay technique, and cGMP measurement. Endothelium-dependent relaxation was attenuated by blocking the $Na^+\;-K^+$ pump in the vascular ring with intact endothelium. In bioassay experiment EDRF release was decreased with the blockade of the $Na^+\;-K^+$ pump in the EDRF donor strip. Endothelium-dependent increase of cGMP level was suppressed by inhibiting the $Na^+\;-K^+$ pump in the test strips. The magnitude of relaxation of test strip which was induced by the perfusate that had passed through the EDRF donor strip was decreased with the blockade of the $Na^+\;-K^+$ pump in the test strip. Therefore, it could be suggested that the attenuation of endothelium-dependent relaxation caused by inhibiting $Na^+\;-K^+$ pump activity is due to both the decreased release of EDRF from endothelial cells and the decreased sensitivity of the smooth muscle cells to EDRF.

• Korean Journal of Veterinary Research
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• v.37 no.1
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• pp.119-128
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• 1997

The relaxation of gastric fundus smooth muscles is the primary physiological event which induces the receptive relaxation of monogastric animals. L-arginine/Nitric oxide(L-arg/NO) system is known to mediate the inhibitory non-adrenergic non-cholinergic(NANC) neurotransmission in various tissues including gastrointestinal smooth muscles. The longitudinal smooth muscles of porcine gastric fundus showed fast relaxation during electrical field stimulation(EFS) and rebound contraction after EFS in NANC condition. So, the purpose of present study was elucidation of the neurotrasmitters related to the NANC relaxation and explanation of the relation between NANC relaxation and L-arg/NO system. The longitdinal smooth muscles of porcine gastric fundus were hung in the organ bath and under the presence of guanethidine($5{\times}10^{-5}M$), precontraction was induced by carbachol($1{\times}10^{-6}M$). The muscle responses to EFS and drugs were isomerically recorded. The rusults were summarized as follows. 1. The longtudinal muscles of porcine gastric fundus showed frequency-dependent relaxation and rebound contraction to electrical field stimulaton(1ms, 8V, 1~16Hz, 20sec, EFS). These responses were blocked by tetrodotoxin($1{\times}10^{-6}M$). 2. The relaxation and rebound contraction of the longitudinal muscles of porcine gastric fundus to EFS were inhibited by L-NAME($2{\times}10^{-5}M$). The inhibitory effect of L-NAME was antagonized by L-arginine($1{\times}10^{-3}M$), but not by D-arginine($1{\times}10^{-3}M$). 3. Exogenous NO($NaNO_2$, $1{\times}10^{-5}{\sim}1{\times}10^{-4}M$, pH=2.0) caused concentration-dependent relaxation as EFS did. 4. Methylene Blue($2{\times}10^{-5}M$), a soluble guanylate cyclase inhibitor, inhibited the relaxation and rebound contraction of the longitudinal muscles of porcine gastric fundus induced by EFS, but N-ethlmaleimide, a adenylate cyclase inhibitor, did not. 5. 8-Br-cGMP($1{\times}10^{-6}{\sim}3{\times}10^{-6}M$), permeable cGMP analogue, induced dose-dependent relaxation. but 8-Br-cAMP($1{\times}10^{-6}{\sim}3{\times}10^{-6}M$), permeable cAMP analogue, did not. Both did not evoked rebound contraction. 6. ${\alpha}$-chymotrypsin did not affect the relaxation of the longitudinal muscles of porcine gastric fundus. 7. Reactive blue 2($1{\times}10^{-4}M$, 40min) siginificantly inhibited the rebound contraction induced by EFS and inhibited contraction caused by exogenous ATP($1{\times}10^{-4}{\sim}1{\times}10^{-3}M$). These results suggests that NANC relaxation of the longitudinal muscles of porcine gastric fundus mainly mediated by NO and the rebound contraction is related to NO and other neurotransmitters.

• The Korean Journal of Physiology
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• v.22 no.1
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• pp.13-29
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• 1988

In order to elucidate the regulatory mechanism of intracellular calcium ion concentrations, contractions or contractures induced by $Na^{+}-removal$, calcium-application or ouabain-treatment as an index of $Na^+/Ca^{2+}$ exchange activity were studied in atrial muscle or vascular smooth muscle (aorta and renal artery) of the rabbit. The magnitude of low sodium contractures in atrial trabeculae increased with sigmoid shape when external sodium concentrations were reduced to sodium-free condition, whereas that of calcium contracture intensified in a parabolic pattern when external calcium concentrations were elevated to 8 mM. $Na^{+}-removal$ contractures were induced in a duration-dependent manner to $K^{+}-free$ exposure and same findings were observed with ouabain treatment. $Na^{+}-free$ contractures were not affected by verapamil treatment, but stimulated by $100{\mu}M\;Mn^{2+}$ and inhibited by high concentrations of $Mn^{2+}\;(2{\sim}8mM)$ in a dose-dependent manner. Ryanodine which is known to suppress the release of calcium from internal store abolished spontaneous twitch contractions induced by $K^{+}-free$ solution, but had no effect on the development $Na^{+}-free$ contractures. Na-free contractures were not always induced in vascular smooth muscle preparations. Contractures by $O\;mM\;Na^+$ were usually seen in aorta, but not often in renal artery.$50\;mM\;K^+$, noradrenaline (NA) and angiotensin II (AII) always evoked very large contraction in all preparations of vascular smooth muscle. Contractures developed by $O\;mM\;Na^+$ were not sensitive to verapamil treatment as in atrial trabeculae, but were abolished by $100{\mu}M\;Mn^{2+}$. In contrast to $Na^{+}-free$ contractures, $Mn^{2+}(100{\mu}M)$ had no effect on the contractures induced by NA or 50 mM$K^+$. Caffeine in the concentration of 10 mM evoked transient contracture in the distal renal artery. The rate of spontaneous relaxation in caffeine contracture was dependent upon the concentrations of external sodium, and had double component of relaxation when the rate of relaxation was plotted in the semilogarithmic scale of relative tension versus time. Especially late components of relaxation had more direct relation to $Na^+$ concentrations. It could be concluded that $Na^+/Ca^{2+}$ exchange mechanism in the heart has a large capacity, inhibited by $Mn^{2+}$ but not by verapamil and ryanodine, while $Na^+/Ca^{2+}$ exchange system in vascular smooth muscle has a very low capacity especially in small artery, inhibited by low concentration of $Mn^{2+}\;(100{\mu}M)$ but not affected by verapamil and ryanodine.

• The Korean Journal of Physiology
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• v.29 no.1
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• pp.61-67
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• 1995

The extract of Ginkgo bibloba (EGb) is a complex mixture of natural products from the Ginkgo leaves and clinically used for the treatment of cerebral and peripheral circulatory disturbances due to its combined activity of several vasoactive principles. In this study we investigated the action of EGb and its mechanism in isolated rabbit corporal smooth muscle to evaluate the possibility of using this material as a pharmacoerecting agent. Strips of rabbit corpus cavernosum were mounted in organ chambers to measure isometric tension. EGb began to exert an relaxing effect at 1 mg/ml in the submaximally precontracted muscle strips with phenylephrine $(PHE,\;5{\times}10^{-6}\;M)$; causing concentration-dependent relaxation with maximal effect at $3{\sim}5\;mg/ml$. That relaxation was partially inhibited by removal of the smooth muscle endothelium or by pretreatment with a NO scavenger, pyrogallol $(10^{-4}\;M)$ or the guanylate cyclase inhibitor, methylene blue $(10^{-4}\;M)$. Pretreatment with EGb (3 mg/ml) inhibited PHE- $(5{\times}10^{-6}\;M)$ or KCI- (20 and 40 mM) induced contraction of muscle strip. In calcium-free high potassium solution EGb depressed the basal tone of the depolarized muscle strip and inhibited calcium-induced contraction when $CaCl_2$ $(10^{-4}\;M)$ was added. These results suggest that EGb relaxes rabbit corpus cavernosal smooth muscle through multiple action mechanisms that include increasing the release of nitric oxide from the corporal sinusoidal endothelium, sequestration of intracytosolic calcium, and maybe a hyperpolarizing action.

• Korean Journal of Pharmacognosy
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• v.17 no.1
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• pp.12-18
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• 1986

In order to investigate experimentally the clinical effects of Choweesungchung-Tang that has been widely used in the cardiovascular and neuropsychogenic disease, experimental studies with experimental animals were carried out. The results of these studies were summarized as follows; Suppressive action was not shown on the convulsion induced by strychnine, but significant effect was noted on the convulsion induced by picrotoxin and caffeine. In acetic acid method, analgesic effect was noted. By the rotor rod and wheel cage method, sedative action was noted. A prolongation of hypnotic time induced by pentobarbital-Na was obtained. Relaxing action was noted remarkably on the ileum of mice, also about mice and guinea-pigs, the same effect was recognized on the smooth muscle of the ileum. The expansion of blood vessels by relaxation of smooth muscle and hypotensive action were noted.

• Korean Journal of Veterinary Service
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• v.17 no.3
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• pp.255-263
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• 1994

To elucidate the action of the adrenergic nerve on the isolated uterine smooth muscle of the pig, effects of electrical transmural nerve stimulation and norepinephrine were investigated on the pretreatment of phentolamine ； non-selective ${\alpha}$-adrenoceptor blocker, propranolol ; ${\beta}$-adrenoceptor blocker and the yohimbine；${\alpha}_2$-selective adrenoceptor blocker from physiograph. 1. The relaxation response induced by norepinephrine was the concentration of $10^{-6}$ M at first and maximum response was concentration of $10^{-4}$M. 2. The relaxation response induced by norepinephrine was not effected by the pretreatment with non-selective $\alpha$-adrenoceptor blocker, phentolanune ($10^{-6}$ M) but was completely blocked by the pretreatment with ${\beta}$-adrenoceptor blocker, propranolol($10^{-6}$ M). 3. The contractile response induced by electrical transmural nerve stimulation(20V, 10Hz, 0.5msec, 20sec ) was inhibited by the pretreatment with non-selective ${\alpha}$-adrenoceptor blocker, phentolamine($10^{-6}$ M) but was not inhibited and rather increased by the pretreatment ${\beta}$-adrenoceptor blocker, propranolol($10^{-6}$ M), and was not approximately effected by the pretreatment with ${\alpha}_2$-adrenoceptor blocker, yohimbine($10^{-6}$ M). These finding suggest that it was excitatory action by ${\alpha}_1$-adrenergic nerve and inhibitory action by ${\alpha}_2$-adrenergic, ${\beta}$-adrenergic nerve on uterine smooth muscle of the pig.

• Journal of Life Science
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• v.10 no.6
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• pp.584-590
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• 2000

Natural products are one of the useful source of cardiovascular drugs, in particular, when they have antioxidant activity. Gagaminine, an alkaloid isolated from the roots of Cynanchum wilfordi Hemsley, has been reported to potently inhibit the aldehyde oxidase activity ({TEX}$IC_{50}${/TEX}=0.8$\mu$M) and reduce lipid peroxidation. However, the effect of gagaminine on vascular smooth muscle has not yet been investigated. In the present study, we examined whether gagaminine relaxes vascular smooth muscle by isometric tension study. In order to observe its relaxation effect on the arteries, conductivel vessel (rat thoracic aorta) and resistance vessel (pig coronary artery) were purposely used. Results indicated that gagaminine relaxed in a concentration-dependent manner $\alpha$-adrenoceptor agonist, phenylephrine (PE)-induced contraction of rat aorta. Pretreatment with gagaminine inhibited PE-induced contraction, noncompetitively. {TEX}$Ca^{2+}${/TEX}-induced contraction was significantly diminished by gagaminine. In pig coronary artery, gagaminine relaxed thromboxane receptor (U 46619)-mediated contraction in dose-dependent manner. Pretreatment with gagaminine also reduced the maximum contraction induced by KCl. These observations strongly suggest that agagminnine relaxes vascular smooth muscle, irrespective of both resistance and conductive artery. We demonstrate that gagaminine, a potent natural antioxidant, has a significant vasodilatory effect and its action mechanism van be ascribed at least in part to {TEX}$Ca^{2+}${/TEX} antagonistic action as evidenced by inhibition {TEX}$Ca^{2+}${/TEX}-induced contraction (rat aorta) and KCl-induced contraction (porcine artery). Furthermore, neither $\alpha$ -adrenoceptor nor thromboxane receptor seems responsible for the relaxation of gagaminine.

• Mycobiology
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• v.48 no.2
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• pp.153-156
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• 2020

Calvatia nipponica, a puffball mushroom (Agaricaceae), is thought to be an aphrodisiac, as this mushroom is traditionally known to improve sexual function in males. As part of the systematic study to determine the bioactive secondary metabolites from C. nipponica responsible for aphrodisiac effects, chemical analysis of methanol (MeOH) extracts of the fruiting bodies of C. nipponica resulted in the isolation of two major compounds: N,N-dimethyl-anthranilic acid (1) and (7Z,10Z)-7,10-octadecadienoic acid methyl ester (2). Compounds 1 and 2 were evaluated for cumulative dose-dependent relaxation responses to precontracted penile corpus smooth muscle (PCCSM). Results show that compounds 1 and 2 exhibited a maximum relaxation effect of 20.33 ± 2.18% and 24.63 ± 3.60%, respectively. These findings indicate that compounds 1 and 2, major components of C. nipponica, could potentially be used to treat erectile dysfunction, functioning as natural aphrodisiacs.