• 약학회지
• /
• 제54권5호
• /
• pp.392-397
• /
• 2010

The aim of present study was to investigate the possible influence and related mechanism of additional alcohol on the flavonoid- induced arterial relaxation. Agonist-induced vascular smooth muscle contractions involve the activation of thick or thin filament pathway. However, there are no reports addressing the question whether this pathway is involved in quercetin-induced relaxation cotreated with alcohol in rat aortae contracted with phorbol ester, fluoride or thromboxane $A_2$ mimetic U-46619. We hypothesized that cotreated alcohol plays a role in vascular relaxation evoked by quercetin in rat aortae. Endothelium-denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Quercetin inhibited phorbol ester, fluoride or thromboxane $A_2$-induced contraction regardless of endothelial function. However, alcohol didn't decrease any agonist-induced contraction. Interestingly, only in thromboxane $A_2$-induced contraction, synergistic results were observed in aortae denuded and cotreated with quercetin and alcohol suggesting that additional pathways different from antioxidation or endothelial nitric oxide synthesis might be involved in the vasorelaxation. In conclusion, in the agonists-contracted rat aortae, quercetin and alcohol together showed synergistic response regardless of endothelial function in an agonist-dependent manner.

• 약학회지
• /
• 제50권4호
• /
• pp.293-299
• /
• 2006

The aim of present study was to investigate the possible influence of Rho-kinase inhibition on the plant-derived estrogen-like compounds-induced arterial relaxation. Agonist- or depolarization-induced vascular smooth muscle contractions involve the activation of Rho-kinase pathway. However there are no reports addressing the question whether this pathway is involved in genistein-or daidzein-induced vascular relaxation in rat aortae precontracted with phenylephrine or thromboxane $A_2$ mimetic U-46619. We hypothesized that Rho-kinase inhibition plays a role in vascular relaxation evoked by genistein or daidzein in rat aortae. Endothelium-intact and denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Genistein concentration-dependently inhibited phenylephrine or thromboxane $A_2-induced$ contraction regardless of endothelial function. Surprisingly, in the agonists-induced contraction, similar results were also observed in aortae treated with daidzein, the inactive congener for protein tyrosine kinase inhibition, suggesting that Rho-kinase might act upstream of tyrosine kinases in phenylephrine-induced contraction. In conclusion, in the agonists-precontracted rat aortae, genistein and daidzein showed similar relaxant response regardless of tyrosine kinase inhibition or endothelial function.

• 대한동의생리학회:학술대회논문집
• /
• 대한동의생리학회 2005년도 하계학술대회
• /
• pp.18-18
• /
• 2005

• The Korean Journal of Physiology and Pharmacology
• /
• 제18권6호
• /
• pp.489-495
• /
• 2014

Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ${\omega}$-conotoxin GVIA (CgTx), a selective N-type $Ca^{2+}$ channel ($I_{Ca-N}$) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ${\omega}$-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of $I_{Ca-N}$ which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.

• 대한수의학회지
• /
• 제44권3호
• /
• pp.389-397
• /
• 2004

The therapeutic efficacy of xylamine in the field of psychological medicine has been recognized for years and the drug is used to treat depression and some other conditions, but little is known about its mechanism of action on vascular system. Therefore, the present study was designed to investigate the influence of xylamine on the contractile responses of isolated rat thoracic arteries to phenylephrine(PE) and potassium chloride(KCl). Xylamine produced a concentration-dependent relaxation in PE-precontracted endothelium intact(+E) rat aortic rings, but not in a KCl-precontracted aortic rings. Also, xylamine inhibited the PE-induced contraction in concentration-dependent manner, but not in the high KCl-induced contraction in +E rings. This concentration-dependent inhibition was suppressed by the removal of the endothelium (-E). The inhibitory effects of xylamine($0.3{\mu}M$) on the PE-induced contractions were suppressed by N(G)-nitro-L-arginine(L-NNA), N(omega)-nitro-L-arginine methyl ester(L-NAME), aminoguanidine, dexamethasone, methylene blue, 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one(ODQ), indomethacin, ryanodine, tetrabutylammonium(TBA), lidocaine, procaine and 0 mM extracellular $Na^+$, but not by 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate(NCDC), lithium, nifedipine, verapamil, 0 mM extracellular $Ca^{2+}$, glibenclamide and clotrimazole. These findings suggest that xylamine could act as a vasorelaxant and direct inhibitor of arterial contraction. This vasorelaxation involves an endothelial nitric oxide (NO)/cGMP (guanosine 3',5'-cyclic monophosphate) pathway or cyclooxygenase system, and an interference with $Ca^{2+}$ release, TBA-sensitive $Ca^{2+}$-activated $K^+$ channels and $Na^+$$ channels.

• The Korean Journal of Physiology
• /
• 제21권2호
• /
• pp.191-200
• /
• 1987

The activation mechanism of the sustained contractions induced by norepinephrine and K-depolarization was studied in renal vascular muscle. Helical strips of arterial muscle were prepared from rabbit renal arteries. All experiments were performed in Tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C$. Renal arterial muscles developed a contracture rapidly when exposed to a 40 mM K-Tyrode solution. In the absence of external $Ca^{2+}$, however, no K-contracture appeared. The contracture induced by K-depolarization was abolished by the treatment with $Ca^{2+}-antagonist\;(verapamil)$ or lanthanum $(La^{3+})$. From these results, it is obvious that K-contracture of renal arterial strip required $Ca^{2+}$ in the medium and this contracture was developed by the increased $Ca^{2+}-influx$ due to K-depolarization. Noradrenaline (5 mg/l) induced also a similar sustained contraction rapidly in all strips. Even on the K-contracture and in $Ca^{2+}-free$ Tyrode solution and also in the Tyrode solution pretreated with verapamil or $La^{3+}$, noradrenaline produced a contraction. However, the contraction in $Ca^{2+}-free$ Tyrode solution was not sustained and decreased gradually. The amplitude of noradrenaline-induced contracture was dependent on external $Ca^{2+}$; The contracture increased dose-dependently, but over 3 mM $Ca^{2+}$, decreased. The results of this experiment suggest that K-contracture was developed by an increased $Ca^{2+}-influx$ due to membrane depolarization, while noradrenaline-induced contracture was developed by both transmembrane $Ca^{2+}-influx$ and the mobilizaiton of cellular $Ca^{2+}$

• 대한한방내과학회지
• /
• 제21권1호
• /
• pp.23-30
• /
• 2000

Objectives : To analyze the effects of Samul-Tang and combinations of constituent herbs on arterial contraction. Method : In order to investigate the effects, Angelicae gigantis Radix, Cnidii Rhizoma, Rehmanniae Radix, Paeoniae Radix, in which one of them, three of them, and all of them, were used to exam. Results : Samul-Tang significantly inhibited the contraction of artery induced by PE(phenylephrine), accordingly as the concentration of Samul-Tang increased and inhibited in both with intact and removed endothelium. Among the constituent herbs of Samul-Tang, Paeoniae Radix and Paeoniae Radix-Cnidii Rhizoma combination inhibited the PE-induced contraction of artery the most. Conclusions : Samul-Tang and constituent herbs of Samul-Tang inhibit the contraction of artery.

• The Korean Journal of Physiology
• /
• 제28권2호
• /
• pp.159-167
• /
• 1994

The contraction of rabbit basilar artery was examined as a function of changes in the $Na^+$ electrochemical gradient in order to determine the contribution of $Na^+/Ca^{2+}$ exchange to the modulation of contractility. Ouabain $(10^{-5}\;M)$ or $K^+-free$ Tyrode solution caused an increase in tonic tension even in the presence of a $Ca^{2+}$ channel blocker $(10^{-6}\;M\;verapamil)$ and an ${\alpha}-receptor$ blocker $(10^{-5}\;M\;phentolamine)$. After treatment with ouabain $(10^{-5}\;M)$, contractions were augmented by reduction of external $Na^+$ concentration. The longer the treatment with ouabain $(10^{-5}\;M)$ was, the larger the amplitude of $Na^+-free$ contracture was. $Na^+-free$ contracture wag induced by either substitution of equimolar Tris for $Na^+$ or substitution of equimolar $Li^+\;for\;Na^+$. The competition between $Na^+\;and\;Ca^{2+}$ for the $Na^+/Ca^{2+}$ exchange carrier would exist, because it was observed that contractility was dependent on the $Na^+$ electrochemical gradient or the extracellular $Ca^{2+}$ concentration (2 mM, 4 mM). Ryanodine $(10^{-7}\;M)$, the blocker of intracellular $Ca^{2+}$ release from the sarcoplasmic reticulum, did not suppress the development of $Na^+-free$ contracture. The contractile response to norepinephrine $(10^{-6}\;M)$ was augmented by reducing the extracellular $Na^+$ concentration. The relaxation rate from caffeine-induced contraction was dependent on the extracellular $Na^+$ concentration (0 mM, 140 mM). From the above results, it could be suggested that $Na^+/Ca^{2+}$ exchange can move $Ca^{2+}$ either into or out of rabbit basilar arterial smooth muscle. $Ca^{2+}$ entry or extrusion is dependent upon the $Na^+$ electrochemical gradient. $Na^+/Ca^{2+}$ exchange plays a significant role in the regulation of contractility in rabbit basilar arterial smooth muscle.

• The Korean Journal of Physiology and Pharmacology
• /
• 제13권4호
• /
• pp.287-293
• /
• 2009

The dried roots of Danshen (Salvia miltiorrhiza) and Sanchi (Panax notoginseng) have been widely used in traditional Chinese medicine for promoting blood circulation as well as various other bodily functions. Here we investigated the effects of a mixture of aqueous extracts of Danshen and Sanchi, named PASEL, on blood pressure and vascular contractility in rats. Orally administered PASEL (62.5 mg/kg and 250 mg/kg, for 5 weeks) lowered the blood pressure of spontaneous hypertensive rats (SHR) but this was not observed in normal Wistar-Kyoto rats (WKR). We then investigated the effects of PASEL on the arterial contraction of the small branches of cerebral arteries (CAs) and large conduit femoral arteries (FAs) in rats. PASEL did not affect high-K (KCI 60 mM)- or phenyleprine (PhE)-induced contracture of FAs. The myogenic response, a reactive arterial constriction in response to increased luminal pressure, of small CA was dose-dependently suppressed by PASEL in SHR as well as control rats. Interestingly, the KCI-induced contraction of small CAs was slowly reversed by PASEL, and this effect was more prominent in SHR than control WKR. PASEL did not inhibit angiotensin-converting enzyme (ACE) activity. These results demonstrated that the antihypertensive effect of PASEL might be primarily mediated by altering the arterial MR, not by direct inhibition of L-type $Ca^{2+}$ channels or by ACE inhibition.

• The Korean Journal of Physiology
• /
• 제29권1호
• /
• pp.39-50
• /
• 1995

This study was designed to clarify the action of cyclic nucleotides, cyclic AMP and cyclic GMP, on phorbol 12,13-dibutyrate (PDBu)-induced contraction in rings isolated from rabbit carotid artery. Arterial rings, 2 mm in width, were myographied isometrically in an isolated organ bath. PDBu produced slowly developing, sustained contraction in rabbit carotid artery, in a dose dependent manner, which was independent of extracellular $Ca^{2+}$ PDBu-induced contraction was relaxed by staurosporine, which suggests that PDBu-induced contraction is mediated by protein kinase C (PKC). $^{45}Ca^{2+}$ uptake by rabbit carotid artery was increased by PDBu during depolarization, but not in control. Isoproterenol and sodium nitroprusside (SNP) relaxed phenylephrine-induced contraction. However, SNP but not isoproterenol relaxed the contraction induced by PDBu. Acetylcholine relaxed PDBu-induced contraction in the presence of the endothelium. 8-bromo-cyclic AMP, a permeable analogue of cyclic AMP, suppressed phenylephrine-induced contraction but not PDBu-induced contraction. 8-bromo cyclic GMP relaxed both of them with dose dependency. A large dose of forskolin relaxed PDBu-induced contraction. PDBu increased cyclic AMP without considerable change in the level of cyclic GMP. Based on these findings, PDBu-induced contraction of rabbit carotid artery was relaxed by cyclic GMP more effectively than cyclic AMP, and the action of cyclic AMP could be mediated by cyclic GMP dependent protein kinase. Therefore it is suggested that the antagonistic action between protein kinase C and cyclic GMP-dependent protein kinase plays a major role in the regulation of vascular tone.