Endothelium-dependent vasodilation by ferulic acid in aorta from chronic renal hypertensive rats

( Seok Choi ),( Hyun Il Kim ),( Sang Hag Park ),( Mi Jung Lee ),( Jae Yeoul Jun ),( Hyun Lee Kim ),( Jong Hoon Chung ),( Cheol Ho Yeum ) 대한신장학회 2012 Kidney Research and Clinical Practice Vol.31 No.3

Background: Ferulic acid (FA) is a naturally occurring nutritional compound. Although it has been shown to have antihypertensive effects, its effects on vascular function have not been intensively established. The aim of this study was to assess the vasoreactivity of FA in chronic two-kidney, one-clip (2K1C) renal hypertensive rats. Methods: Hypertension was induced in 2K1C rats by clipping the left renal artery and age-matched rats that received a sham treatment served as a control. Thoracic aortas were mounted in tissue baths to measure isometric tension. The effects of FA on vasodilatory responses were evaluated based on contractile responses induced by phenylephrine in the aortic rings obtained from both 2K1C and sham rats. Basal nitric oxide (NO) bioavailability in the aorta was determined by the contractile response induced by NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Results: FA induced concentration-dependent relaxation responses which were greater in 2K1C hypertensive rats than in sham-clipped control rats. This relaxation induced by FA was partially blocked by the removal of endothelium or by pretreating with L-NAME. L-NAME-induced contractile responses were augmented by FA in 2K1C rats, while no significant differences were noted in sham rats. FA improved acetylcholine-induced endothelium-dependent vasodilation in 2K1C rats, but not in sham rats. The simultaneous addition of hydroxyhydroquinone significantly inhibited the increase in acetylcholine-induced vasodilation by FA. Conclusion: These results suggest that FA restores endothelial function by altering the bioavailability of NO in 2K1C hypertensive rats. The results explain, in part, the mechanism underlying the vascular effects of FA in chronic renal hypertension.

Imipramine Inhibits A-type Delayed Rectifier and ATP-Sensitive K+ Currents Independent of G-Protein and Protein Kinase C in Murine Proximal Colonic Myocytes

Seok Choi,Shankar Prasad Parajuli,Geon Han Lim,Jin Ho Kim,Cheol Ho Yeum,Pyung Jin Yoon,Jae Yeoul Jun 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.11

The effects of imipramine on A-type delayed rectifier K+ currents and ATP-sensitive K+ (KATP) currents were studied in isolated murine proximal colonic myocytes using the whole-cell patchclamp technique. Depolarizing test pulses between -80 mV and +30 mV with 10 mV increments from the holding potential of -80 mV activated voltage-dependent outward K+ currents that peaked within 50 ms followed by slow decreasing sustained currents. Early peak currents were inhibited by the application of 4-aminopyridine, whereas sustained currents were inhibited by the application of TEA. The peak amplitude of A-type delayed rectifier K+ currents was reduced by external application of imipramine. The half-inactivation potential and the halfrecovery time of A-type delayed rectifier K+ currents were not changed by imipramine. With 0.1 mM ATP and 140 mM K+ in the pipette and 90 mM K+ in the bath solution and a holding potential of –80 mV, pinacidil activated inward currents; this effect was blocked by glibenclamide. Imipramine also inhibited KATP currents. The inhibitory effects of imipramine in A-type delayed rectifier K+ currents and KATP currents were not changed by guanosine 5-O-(2-thiodiphosphate) (GDPβS) and chelerythrine, a protein kinase C inhibitor. These results suggest that imipramine inhibits A-type delayed rectifier K+ currents and KATP currents in a manner independent of G-protein and protein kinase C.

PGE<SUB>2</SUB> Regulates Pacemaker Currents through EP<SUB>2</SUB>-Receptor in Cultured Interstitial Cells of Cajal from Murine Small Intestine

Seok Choi,Kyung Won Cho,Jong-Hyun Reu,Jun-Soo Kim,Hyun Sik Mun,Myung Young Kim,Kwang Chul Park,Gwang Sik Heo,Sung Jong Chang,Cheol Ho Yeum,Pyung Jin Yoon,Jae Yeoul Jun 대한생리학회-대한약리학회 2004 The Korean Journal of Physiology & Pharmacology Vol.13 No.1

The interstitial cells of Cajal (ICCs) are the pacemaker cells in gastrointestinal tract and generate electrical rhythmicity in gastrointestinal muscles. Therefore, ICC may be modulated by endogenous agents such as neurotransmitter, hormones, and prostaglandins (PGs). In the present study, we investigated the effects of prostaglandins, especially PGE<SUB>2</SUB>, on pacemaker currents in cultured ICCs from murine small intestine by using whole-cell patch clamp techniques. ICCs generated spontaneous slow waves under voltage-clamp conditions and showed a mean amplitude of ⁣452⁑39 pA and frequency of 18⁑2 cycles/min (n=6). Treatments of the cells with PGE<SUB>2</SUB> (1μM) decreased both the frequency and amplitude of the pacemaker currents and increased the resting currents in the outward direction. PGE<SUB>2</SUB> had only inhibitory effects on pacemaker currents and this inhibitory effect was dose-dependent. For characterization of specific membrane EP receptor subtypes, involved in the effects of PGE<SUB>2</SUB> on pacemaker currents in ICCs, EP receptor agonists were used: Butaprost (1μM), EP<SUB>2</SUB> receptor agonist, reduced the spontaneous inward current frequency and amplitude in cultured ICCs (n=5). However sulprostone (1μM), a mixed EP<SUB>1</SUB> and EP<SUB>3</SUB> agonist, had no effects on the frequency, amplitude and resting currents of pacemaker currents (n=5). SQ-22536 (an inhibitor of adenylate cyclase; 100μM) and ODQ (an inhibitor of guanylate cyclase; 100μM) had no effects on PGE<SUB>2</SUB> actions of pacemaker currents. These observations indicate that PGE<SUB>2</SUB> alter directly the pacemaker currents in ICCs, and that the PGE<SUB>2</SUB> receptor subtypes involved are the EP<SUB>2</SUB> receptor, independent of cyclic AMP- and GMP-dependent pathway.

Mechanism of Ca2+ -activated Cl- Channel Activation by Ginsenosides in Xenopus Oocytes

Seok Choi,Se Yeon Jung,Seong Hwan Rho,Sung Ryong Ko,Hye Won Rhim,Chul Seung Park,Seung Yeol Nah 고려인삼학회 2000 Journal of Ginseng Research Vol.24 No.4

Spinal Co-Administration of Ginsenosides with Morphine Prevents the Development of Opioid Tolerance and Attenuates Opioid Dependence

Seok Choi,Se Yeon Jung,Jin Ju Nah,Eun Soon Ahn,Yoon Hee Kim,Ki Yeul Nam,Seok Chang Kim,Sung Ryong Ko,Hye Whon Rhim,Seung Yeol Nah 고려인삼학회 1999 Journal of Ginseng Research Vol.23 No.4

Effect of Ginsenosides, Active Components of Ginseng, on Capsaicin-Induced Pain-Related Behavior

Seok Choi,Se-Yeon Chung,Seung-Yeol Nah 한국실험동물학회 2000 한국실험동물학회 학술발표대회 논문집 Vol.2000 No.-

Effects of Pine Needle Extract on Pacemaker Currents in Interstitial Cells of Cajal from the Murine Small Intestine

Seok Choi,정현숙,Dilli Parasad Paudyal,Jae Yeoul Jun,Cheol Ho Yeum,Pyung Jin Yoon,Chan Guk Park,Man Yoo Kim,Insuk So,Ki Whan Kim 한국분자세포생물학회 2005 Molecules and cells Vol.20 No.2

Extracts of pine needles (Pinus densiflora Sieb. et Zucc.) have diverse physiological and pharmacological actions. In this study we show that pine needle extract alters pacemaker currents in interstitial cells of Cajal (ICC) by modulating ATP-sensitive K+ channels and that this effect is mediated by prostaglandins. In whole cell patches at 30°C, ICC generated spontaneous pacemaker potentials in the current clamp mode (I = 0), and inward currents (pacemaker currents) in the voltage clamp mode at a holding potential of –70 mV. Pine needle extract hyperpolarized the membrane potential, and in voltage clamp mode decreased both the frequency and amplitude of the pacemaker currents, and increased the resting currents in the outward direction. It also inhibited the pacemaker currents in a dose-dependent manner. Because the effects of pine needle extract on pacemaker currents were the same as those of pinacidil (an ATP-sensitive K+ channel opener) we tested the effect of glibenclamide (an ATPsensitive K+ channels blocker) on ICC exposed to pine needle extract. The effects of pine needle extract on pacemaker currents were blocked by glibenclamide. To see whether production of prostaglandins (PGs) is involved in the inhibitory effect of pine needle extract on pacemaker currents, we tested the effects of naproxen, a non-selective cyclooxygenase (COX-1 and COX-2) inhibitor, and AH6809, a prostaglandin EP1 and EP2 receptor antagonist. Naproxen and AH6809 blocked the inhibitory effects of pine needle extract on ICC. These results indicate that pine needle extract inhibits the pacemaker currents of ICC by activating ATP-sensitive K+ channels via the production of PGs.

Mechanisms of phytoestrogen biochanin A-induced vasorelaxation in renovascular hypertensive rats

( Seok Choi ),( Won Suk Jung ),( Nam Soo Cho ),( Kwon Ho Ryu ),( Jae Yeoul Jun ),( Byung Chul Shin ),( Jong Hoon Chung ),( Cheol Ho Yeum ) 대한신장학회 2014 Kidney Research and Clinical Practice Vol.33 No.4

Background: The plant-derived estrogen biochanin A is known to cause vasodilation,but its mechanism of action in hypertension remains unclear. This study wasundertaken to investigate the effects and mechanisms of biochanin A on thethoracic aorta in two-kidney, one clip (2K1C) renovascular hypertensive rats. Methods: Hypertension was induced by clipping the left renal artery, and controlage-matched rats were sham treated. Thoracic aortae were mounted in tissue bathsto measure isometric tension. Results: Biochanin A caused concentration-dependent relaxation in aortic ringsfrom 2K1C hypertensive and sham-treated rats, which was greater in 2K1C rats thanin sham rats. Biochanin A-induced relaxation was significantly attenuated byremoving the endothelium in aortic rings from 2K1C rats, but not in sham rats. Nω-Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, or indomethacin,a cyclooxygenase inhibitor, did not affect the biochanin A-induced relaxation inaortic rings from 2K1C and sham rats. By contrast, treatment with glibenclamide, aselective inhibitor of adenosine triphosphate-sensitive Kþ channels, or tetraethylammonium,an inhibitor of Ca2þ-activated Kþ channels, significantly reducedbiochanin A-induced relaxation in aortic rings from both groups. However,4-aminopyridine, a selective inhibitor of voltage-dependent Kþ channels, inhibitedthe relaxation induced by biochanin A in 2K1C rats, whereas no significantdifferences were observed in sham rats. Conclusion: These results suggest that the enhanced relaxation caused by biochaninA in aortic rings from hypertensive rats is endothelium dependent. Vascularsmooth muscle Kþ channels may be involved in biochanin A-induced relaxation inaortae from hypertensive and normotensive rats. In addition, an endotheliumderivedactivation of voltage-dependent Kþ channels contributes, at least in part, tothe relaxant effect of biochanin A in renovascular hypertension.

Direct vascular actions of quercetin in aorta from renal hypertensiverats

( Seok Choi ),( Kwon Ho Ryu ),( Sang Hag Park ),( Jae Yeoul Jun ),( Byung Chul Shin ),( Jong Hoon Chung ),( Cheol Ho Yeum ) 대한신장학회 2016 Kidney Research and Clinical Practice Vol.35 No.1

Background: Chronic treatment with the dietary flavonoid quercetin is known to lower blood pressure and restore endothelial dysfunction in animal models of hypertension. This study investigated the direct effects of quercetin on vascular response in chronic 2-kidney, 1-clip (2K1C) renal hypertensive rats. The effects of antioxidant vitamin ascorbic acid on the vasoreactivity were also examined. Methods: 2K1C renal hypertension was induced by clipping the left renal artery; age-matched rats that received sham treatment served as controls. Thoracic aortae were mounted in tissue baths for the measurement of isometric tension. Results: Relaxant responses to acetylcholine were significantly attenuated in 2K1C rats in comparison with sham rats. Quercetin or ascorbic acid augmented acetylcholine-induced relaxation in 2K1C rats, whereas no significant differences were noted in sham rats. The relaxation response to sodium nitroprusside was comparable between 2K1C and sham rats, and sodium nitroprussideeinduced relaxation was not altered by quercetin or ascorbic acid in either group. The contractile response to phenylephrine was significantly enhanced in 2K1C rats compared with sham rats. Phenylephrine-induced contraction was inhibited by pretreatment with quercetin or ascorbic acid in 2K1C rats, whereas neither chemical affected responses in sham rats. Nw-nitro-L-arginine methyl ester markedly augmented the contractile response to phenylephrine in sham rats, whereas no significant differences were observed in 2K1C rats. Quercetin or ascorbic acid did not affect phenylephrine-induced contraction in the presence of Nw-nitro-L-arginine methyl ester in either 2K1C or sham rats. Conclusion: Acute exposure to quercetin appears to improve endotheliumdependent relaxation and inhibit the contractile response, similar to the effect of ascorbic acid in 2K1C hypertension. These results partially explain the vascular beneficial effects of quercetin in renal hypertension.

Direct Vascular Actions of Indapamide in Aorta from Renal Hypertensive Rats

( Seok Choi ),( Hee Wook Whi ),( Mi Jung Lee ),( Jae Yeoul Jun ),( Hyun Lee Kim ),( Jong Hoon Chung ),( Hye Rang Shin ),( Hyun Jung Oh ),( Cheol Ho Yeum ) 대한신장학회 2011 Kidney Research and Clinical Practice Vol.30 No.5

Purpose: Thiazide diuretics exert their hypotensive efficacy through a combined vasodilator and diuretic effect. The present study was conducted to assess the inhibitory effect of thiazide diuretic, hydrochlorothiazide, and the thiazide-like diuretics, indapamide and chlorthalidone on contractile responses to norepinephrine and arginine vasopressin in aortic rings from 2K1C renal hypertensive and sham-clipped normotensive rats. Methods: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Changes in the tension of aortic ring preparations were measured isometrically. Results: Indapamide inhibits the contractile responses to norepinephrine and vasopressin in aortic rings from 2K1C rats, while it did not modify in control rats. The inhibitory effect of indapamide was abolished by endothelium removal. Hydrochlorothiazide or chlorthalidone did not affect the vasoconstriction induced by norepinephrine and vasopressin either in sham or in 2K1C hypertensive rats. Conclusion: These results suggest that indapamide inhibits the contractile responses to norepinephrine and vasopressin via an endothelium-dependent mechanism in 2K1C renal hypertension.