• Journal of Chest Surgery
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• v.46 no.1
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• pp.14-21
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• 2013

Background: Reactive oxygen species (ROS) are known to be related to cardiovascular diseases. Many studies have demonstrated that angiotensin-converting enzyme inhibitors have beneficial effects against ROS. We investigated the antioxidant effect of captopril and enalapril in nitric oxide mediated vascular endothelium-dependent relaxations. Materials and Methods: Isolated rabbit abdominal aorta ring segments were exposed to ROS by electrolysis of the organ bath medium (Krebs-Henseleit solution) after pretreatment with various concentrations (range, $10^{-5}$ to $3{\times}10^{-4}$ M) of captopril and enalapril. Before and after electrolysis, the endothelial function was measured by preconstricting the vessels with norepinephrine ($10^{-6}$ M) followed by the cumulative addition of acetylcholine (range, $3{\times}10^{-8}$ to $10^{-6}$ M). The relevance of the superoxide anion and hydrogen peroxide scavenging effect of captopril and enalapril was investigated using additional pretreatments of diethyldithiocarbamate (DETCA, 0.5 mM), an inhibitor of Cu/Zn superoxide dismutase, and 3-amino-1,2,4-triazole (3AT, 50 mM), an inhibitor of catalase. Results: Both captopril and enalapril preserved vascular endothelium-dependent relaxation after exposure to ROS in a dose-dependent manner (p<0.0001). Pretreatment with DETCA attenuated the antioxidant effect of captopril and enalapril (p<0.0001), but pretreatment with 3AT did not have an effect. Conclusion: Both captopril and enalapril protect endothelium against ROS in a dose-dependent fashion in isolated rabbit abdominal aortas. This protective effect is related to superoxide anion scavenging.

• The Journal of Korean Medicine
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• v.19 no.2
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• pp.228-243
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• 1998

This study was undertaken to evaluate the effect of Sunghyangchungisan (SHCS) on the regulation of vascular tone. Vascular rings isolated from rabbit carotid artery were myographed isometrically in isolated organ baths and the effect of SHCS on contractile activities were determined. SHCS relaxed the arterial rings which were pre-contracted by phenylephrine(PE). The responses to SHCS were partially dose-dependent at concentrations lower than 0.5 mg/ml. When SHCS was applied prior to the exposure to PE, it inhibited the PE-induced contraction by a similar magnitude which was comparable to the relaxation of pre-contracted arterial rings. Washout of SHCS after observing its relaxant effect resulted in a full recovery of PE-induced contractions, indicating that the action mechanism is reversible. The observation that SHCS did not change the $ED_{50}$ of PE on its dose-response curve ruled out the possible interaction of SHCS and ${\alpha}-receptor$. The relaxant effect of SHCS was not affected by removal of endothelium, and pretreatment of the arterial rings with methylene blue or nitro-L-arginine. This results suggest that the action of SHCS is not mediated by endothelium nor soluble guanylate cyclase. SHCS relaxed high $K^{+}-induced$ contractions as well, whereas it failed to relax phorbol ester-induced contractions. When contraction was induced by additive application of $Ca^{2+}$ in arterial rings which were pre-depolarized by high $K^+$ in a $Ca^{2+}-free$ solution, the relaxant effect of SHCS was attenuated by increasing the $Ca^{2+}$ concentration. SHCS, when applied to the arterial rings pre-contracted by PE and then relaxed by nifedipine, a $Ca^{2+}$ channel blocker, did not show additive relaxation. From above results, it is suggested that SHCS relax PE-induced contraction of rabbit carotid artery in an endothelium-independent manner, and inhibition of $Ca^{2+}$ influx may contribute to the underling mechanism.

• Journal of Chest Surgery
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• v.29 no.12
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• pp.1299-1305
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• 1996

The rat thoracic aorta was harvested to determine whether either hyperkalemla or hypothermia impairs the endothelium-dependent re axation of the vascular smooth muscle. Isolated thoracic aorta segments were studied in five groups(n=10 in each group). In group I(control), the isolated aortic seglnents were suspended in organ bath without any intervention. In group ll(endotheilum removAl). the endothelium of the aortic segment was removed by gentle rubbing of the intimal surface with a pair of forceps. In group III(457), IV(4mST), and V(3757), the aortic segments were exposed for 45minutes to 4$^{\circ}C$ St. Thomas hospital cardioplegic solution(57 : NaCl, 144.3; KCI, 19.6, MgCl:, 15.7 : CaCl, 2.2 mmol/L).4$^{\circ}C$ modified St. Thomas hospital cardioplegic solution(NaCl, 144.3 : KCI. 140.0 : MgCl:, 15.7; CaCl:. 2.2 mmol/L). and 37$^{\circ}C$ 57, before suspending in the organ bath, respectively. Then, aorta segments were suspended in organ baths(physiologic salt solution, 37$^{\circ}C$, 95% oxygen and 5% carbon dioxide) for Isometric tension recording. The vasodilatation to acetylcholine (10-2 to 10-2mol/L) was not impaired in control, 457, 4mST, nd 3757 groups. The vasodilatation to acetylcholine was impaired in endothelium removal group. The vasodilatation to sodium nitroprusslde (10-2 to 10-2 mol/L) was not impaired in all groups. In conclusion, both hyperkalemia and hypothermia do not alter irreversibly the function of the rondothelium of the thoracic aorta of the rat.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.485-493
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• 2005

We studied the effects of trazodone on arterial blood pressure in anesthesized guinea pigs, and on vascular responses in isolated thoracic aorta. Trazodone produced a concentration-dependent relaxation in phenylephrine-precontracted endothelium intact (+E) rings, but not in a KCl-precontracted aortic rings. These relaxant effects of trazodone on +E rings were significantly greater than those on denuded (-E) rings. The trazodone-induced relaxation was suppressed by glibenclamide and tetrabutylammonium, but not by N(G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME), methylene blue (MB), nifedipine, indomethacin, 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC) and clotrimazole. In vivo, infusion of trazodone elicited a significant decrease in arterial blood pressure. Trazodone-induced blood pressure lowering was markedly inhibited by intravenous pretreatment of prazosin but not by pretreatment of saponin, L-NNA, L-NAME, MB, nifedipine, glibenclamide, clotrimazole and NCDC. In addition, trazodone produced an increase in twitch force of isolated papillary muscle and left ventricular pressure of perfused heart. These findings suggest that the endothelium-independent vasorelaxant effect of trazodone may be explained by activation of $Ca^{2+}$-activated and ATP-sensitive $K^+$ channels, and the hypotensive effect of trazodone is not associated with cardiac contraction.

• Journal of Biomedical Engineering Research
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• v.12 no.3
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• pp.165-170
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• 1991

Many experiments about endothelial cell seeding on artificial vessels were studied and conducted For this one or a combination of the extramatrix was used for the underlying matrix. But we used the whole ECM(extracellular matrix) that made excreated from flbroblasl. In thls study, we obtained human adult omental microvascular endothelium by collagenase digestion and used polyurthane sheets in order to make a new artificial vessel material. We cultured fibroblast on the polyurethane and gelatin - coated polyurethane. After confluent ingrowth we treated the polyure thane with triton in order to destroy the cytoskeleton and nucleus. We observed the preformed extra cellular matrix on the ployurethane and cultured the isolated microvascular endothelium. We also ok served the growth of microvascular endothelium on the polyurethane and gelatin. We conclude that the use of the whole ECM is promising fair as a new underying substrate for endothelial cell seeding on artificial vessels.

• YAKHAK HOEJI
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• v.43 no.6
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• pp.843-850
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• 1999

We investigated whether endothelium-derived NO and endothelin-1 might result enhanced vasoconstriction induced by administration of norepinephrien (NE) at the early stage of one-kidney, one-clip (1K1C) renal hypertensive rats. We also studied the relation ship of renin-angiotensin system (RAS) using rat aorta in this hypothesis. L-NMMA (30$\mu$M) and L-NAME(30${\mu}M$) enhanced vasoconstriction induced by NE in thoracic aorta of control rats. However angiotensin converting enzyme (ACE) inhibitor didn't. The aorta of 1KIC rats showed a singnificantly exaggerated contractile response to NE as compared with control rats. Rub-bing the endothelium abolished this difference. Ach and SNP-induced vasorelaxation show no significant difference between 1KIC and control rats. The treatment of phosphoramidon (10${\mu}M$) and oral administration of captopril (0.05, w/v%) abolished the exaggerated contractile response to NE at early stage of 1KIC rats. These results suggest that the increase of contractile response at the early phase in 1KIC rat is partially involved in the activation of ACE.

• YAKHAK HOEJI
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• v.50 no.3
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• pp.208-213
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• 2006

Rat aortic ring preparations were mounted in organ baths, exposed to sodium cyanide $(0.01{\sim}1.0\;mM)$ for 10 min, and then subjected to contractile agents or relaxants such as acetylcholine, sodium nitroprusside and isoproterenol. Presence of low concentration of sodium cyanide did not affect the contractile response to KCl or phenylephrine in the aortic rings with intact endothelium or endothelium denuded. Sodium nitroprusside but not acetylcholine or isoproterenol augmented phenylephrine-induced intact or denuded vascular contraction in the presence of low concentration of sodium cyanide. In conclusion, this study provides the evidence concerning the potentiating effect of sodium nitroprusside on the contraction induced by phenylephrine in rat aortic rings regardless of endothelial function.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.98-98
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• 2001

It has been suggested that hyperuricemia is related to the development of essential hypertension. Hypertensive patients with hyperuricemia has decreased glomerular filtration activity as compared to normotensive patients with hyperuricemia. These studies indicates uric acid concentrations in blood is associated with hypertension, Probenecid is an uricosuric agent which decreases uric acid reabsorption at the proximal tubule. Recently, we have shown that probenecid exerts anti-hypertensive action in Spontaneously Hypertensive Rats. Considering these results, I have designed a series of experiments to explore potential mechanism of antihypertensive action, of probenecid. In isolated rat thoracic aorta. probenecid significantly prevented phenylephrine-induced contraction of the blood vessel. When endothelium removed blood vessels were used, probenecid produced same effect as the intact blood vessels, indicating that probenecid directly act through the ${\alpha}$ -adrenergic receptor in vascular smooth muscles rather than through endothelium. These results suggest that one of the mechanism of antihypertensive effects of probenecid is due to the direct inhibition of ${\alpha}$ -adrenergic receptor in blood vessels.

• International Journal of Vascular Biomedical Engineering
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• v.1 no.1
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• pp.24-31
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• 2003

As endothelial cells are subject to flow shear stress, it is important to determine the detailed velocity distribution in microvessels in the study of mechanical interactions between blood and endothelium. This paper describes a velocity field of the arteriole in the rat mesentery using an intravital microscope and high-speed digital video system obtained by a highly accurate PIV technique. Red blood cells (RBCs) velocity distributions with spatial resolutions of $0.8{\times}0.8{\mu}m$ were obtained even near the wall in the center plane of the arteriole. By making ensemble-averaged time-series of velocity distributions, velocity profiles over different cross-sections were calculated for comparison. The shear rate at the vascular wall also evaluated on the basis of the ensemble-averaged profiles. It was shown that the velocity profiles were blunt in the center region of the vessel cross-section while they were steep in the near wall region. The wall shear rates were significantly small, compared with those estimated from the Poiseuille profiles.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.57-61
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• 2016

Fisetin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of fisetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Fisetin significantly relaxed fluoride-, thromboxane $A_2$- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, fisetin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of fisetin on agonist-induced vascular contraction regardless of endothelial function.