• BMB Reports
• /
• v.44 no.6
• /
• pp.415-420
• /
• 2011

Diabetes is a well-known independent risk factor for vascular disease. However, its underlying mechanism remains unclear. It has been reported that increased influx of the hexosamine biosynthesis pathway (HBP) induces O-GlcNAcylation of proteins, leading to insulin resistance. In this study, we determined whether or not O-GlcNAc modification of proteins could increase vessel contraction. Using an endothelium-denuded aortic ring, we observed that glucosamine induced OGlcNAcylation of proteins and augmented vessel contraction stimulated by U46619, a thromboxane $A_2$ agonist, via augmentation of the phosphorylation of MLC20$MLC_{20}$, MYPT1(Thr855), and CPI17, but not phenylephrine. Pretreatment with OGT inhibitor significantly ameliorated glucosamine-induced vessel constriction. Glucosamine treatment also increased RhoA activity, which was also attenuated by OGT inhibitor. In conclusion, glucosamine, a product of glucose influx via the HBP in a diabetic state, increases vascular contraction, at least in part, through activation of the RhoA/Rho kinase pathway, which may be due to O-GlcNAcylation.

• The Korean Journal of Physiology and Pharmacology
• /
• v.20 no.5
• /
• pp.441-447
• /
• 2016

Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (${\alpha}_2$-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of $10^{-8}{\sim}10^{-6}mol/L$, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or $3{\times}10^{-9}mmol/L$) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial ${\alpha}_2$-adrenoceptor and nitric oxide synthase.

• The Korean Journal of Pharmacology
• /
• v.24 no.1
• /
• pp.63-70
• /
• 1988

Alterations in splanchnic circulatory hemodynamics along with reactivities to the alpha adrenoceptor agonists were assessed in association with the preventive effects of propranolol 10 days after portal ligation. Decreases in precapillary resistance (Ra) and postcapillary resistance (Rv) along with increases in mesenteric blood flow (MBF) and capillary pressure (CP) were observed in conjunction with an increment of splenic pulp pressure (SPP). Dose-dependent increase in Rv in response to noradrenaline, increases in Ra and RV to adrenaline, and increases in superior mesenteric arterial pressure (SMAP), Ra and Rv to phenylephrine observed in sham group were significantly attenuated by portal vein stenosis. In PPL-3 group (propranolol 3 mg/kg, i.p. three times daily for 10 days), MBF was significantly decreased in association with decrease in mesenteric venous pressure (MVP) when compared with those of protal ligated (PL) group, and decreased Ra and Rv in PL group were recovered toward the values of sham group. Likewise, in PPL-1 group (propranolol 5 mg/kg, i.p. once daily for 10 days), the pressor response of Rv to adrenaline was recovered up to the level of sham group. Thus, it is suggested that decreases in Ra and Rv in association with increases in MBF and CP may have a close relevance to the increased SPP, and the changes in circulatory hemodynamics and vascular reactivities were effectively reversed by longterm propranolol treatment. Based on these results, it is concluded that these changes observed in portal hypertension are closely related with the altered functions of the adrenoceptors in the splanchnic vascular beds.

• Tuberculosis and Respiratory Diseases
• /
• v.40 no.2
• /
• pp.135-146
• /
• 1993

Background: In acute pulmonary embolism it has been postulated that the constriction of bronchi and pulmonary artery secondary to neurohumoral response plays an important role in cardiopulmonary dysfunction in addition to the mechanical obstruction of pulmonary artery. Serotonin is considered as the most important mediator. Positive end expiratory pressure (PEEP) stimulates $PGI_2$ secretion from the vascular endothelium, but its role in acute pulmonary embolism is still in controversy. Methods: To study the cardiopulmonary effect and therapeutic role of Ketanserin, selective antagonist of 5-HT2 receptor, and PEEP in acute pulmonary embolism experimental acute pulmonary embolism was induced in dogs with autologous blood clot. The experimental animals were divided into 3 groups, that is control group, Ketanserin injection group and PEEP application group. Results: Thirty minutes after embolization, mean pulmonary arterial pressure and pulmonary vascular resistance increased and cardiac output decreased. $PaO_2,\;P\bar{v}O_2$ and oxygen transport decreased and physiological shunt and $PaCO_2$ increased. After injection of Ketanserin, comparing with control group, mean pulmonary arterial pressure, pulmonary vascular resistance and physiological shunt decreased, while cardiac output, $PaO_2$ and oxygen transport increased. All these changes sustained till 4 hours after embolization. After PEEP application pulmonary vascular resistance, $PaO_2$ and $PaCO_2$ increased, while physiological shunt, cardiac output and oxygen transport decreased. After discontinuation of PEEP, mean pulmonary arterial pressure and pulmonary vascular resistance decreased and were lower than control group, while $PaO_2$ and cardiac output increased and higher than control group. $PaCO_2$ decreased but showed no significant difference comparing with control group. Conclusion: It can be concluded that Ketanserin is effective for the treatment of acute pulmonary embolism. With PEEP hemodynamic status deteriorated, but improved better than control group after discontinuation of PEEP. Thus PEEP may be applied carefully for short period in acute pulmonary embolism if the hemodynamic status is tolerable.

• Journal of Ginseng Research
• /
• v.26 no.1
• /
• pp.1-5
• /
• 2002

It has been well known that Korea red ginseng has an antihypertensive effect. The antihypertensive effect may be due to its ability to change the peripheral resistance. Change of vascular tone in the resistance-sized artery contribute to the peripheral resistance, thereby regulate the blood pressure. Therefore, we investigated to clarify the vasorelaxing mechanism induced by crude saponin of Korea red ginseng in the resistance-sized mesenteric artery of rats. The resistance-sized mesenteric artery was isolated and cut into a ring. The ring segment was immersed in HEPES-buffered solution and its isometric tension was measured using myograph force-displacement transducer. Crude saponin of ginseng relaxed the mesenmetric arterial rings precontracted with norepinephrine (3$\mu$M) in dose-dependent manner (0.01 mg/㎖ -1 mg/㎖. The relaxation by crude saponin was smaller in endothelium-intact preparation than that in endothelium-denuded preparation. The contraction induced by A23187 or phorbol 12,13-dibutyrate was not affected by crude saponin of ginseng. The vasorelaxing effect of crude saponin of ginseng was significantly attenuated by the increase of the extracellular K$\^$+/ concentration. Crude saponin-induced vasorelaxation was not affected by tetraethylammonium (1 mM), glybenclamide (10$\mu$M), and 4-aminopyridine (0.1 mM) in these preparations. Ba$\^$2+/(10$\mu$M ∼100$\mu$M) markedly reduced the crude saponin-induced vasorelakation dose-dependently. From the above results, we suggest that crude saponin of ginseng may stimulate K$\^$+/ efflux and hyperpolarize the membrane, thereby cause the vasorelaxation in the resistance-sized mesenteric artery of rats.

• Journal of Chest Surgery
• /
• v.23 no.1
• /
• pp.32-40
• /
• 1990

Surgical correction of congenital cardiac defects in infants and children with an elevated pulmonary arterial pressure or pulmonary vascular resistance carries a significant early postoperative mortality. And accurate assessments of cardiac output is critically important in these patients. From April 1988 through September 1989, serial measurements of cardiac index, ratio of pulmonary-systemic systolic pressure, ratio of pulmonary-systemic resistance, central venous pressure, left atrial pressure, and urine output during the first 48 hours after the cardiac operation were made in 30 congenital cardiac defects associated with pulmonary hypertension. Cardiac index showed significant increase only after 24 hour postoperatively and this low cardiac performance in the early postoperative period should be considered when postoperative management is being planned in the risky patients. There were no variables which showed any significant correlation with cardiac index. In 12 cases[40%], pulmonary hypertensive crisis developed during the 48 hours postoperatively, and they were treated with full sedation, hyperventilation with 100 % 0y and pulmonary vasodilator infusion. In all patient with preoperative pulmonary hypertension, surgical placement of a pulmonary artery catheter is desirable to allow prompt diagnosis of pulmonary hypertensive crisis and to monitor subsequent therapy.

• International Journal of Vascular Biomedical Engineering
• /
• v.2 no.2
• /
• pp.16-26
• /
• 2004

The object of this study is to develop a mathematical model of the hemodialysis system including the mechanism of solute kinetics, water exchange and also cardiovascular dynamics. The cardiovascular system model used in this study simulates the short-term transient and steady-state hemodynamic responses such as hypotension and disequilibrium syndrome (which are main complications to hemodialysis patients) during hemodialysis. It consists of a 12 lumped-parameter representation of the cardiovascular circulation connected to set-point models of the arterial baroreflexes, a kinetic model (hemodialysis system model) with 3 compartmental body fluids and 2 compartmental solutes. We formulate mathematically this model in terms of an electric analog model. All resistors and most capacitors are assumed to be linear. The control mechanisms are mediated by the information detected from arterial pressoreceptors, and they work on systemic arterial resistance, heart rate, and systemic venous unstressed volume. The hemodialysis model includes the dynamics of urea, creatinine, sodium and potassium in the intracellular and extracellular pools as well as fluid balance equations for the intracellular, interstitial, and plasma volumes. Model parameters are largely based on literature values. We have presented the results on the simulations performed by changing some model parameters with respect to their basal values. In each case, the percentage changes of each compartmental pressure, heart rate (HR), total systemic resistance (TSR), ventricular compliance, zero pressure filling volume and solute concentration profiles are represented during hemodialysis.

• Natural Product Sciences
• /
• v.29 no.2
• /
• pp.91-97
• /
• 2023

Mangosteen peel extract is a xanthone group, that plays an important role in anti-angiogenesis. This study investigated mangosteen peel extract on cerebral neovascularization in type 2 diabetes mellitus (DM) rats. This study used 36 rats, randomized into six groups: C1 (negative control); C2 (high fat diet (HFD) and mangosteen peel extract at 200 mg/kg BW); C3 (HFD and diabetic); E1, E2, and E3 (HFD, diabetic, and extract at 100, 200, and 400 mg/kg BW respectively). All groups were measured body mass index (BMI), homeostasis model assessment-insulin resistance (HOMA-IR) and β cell function (HOMA-B), and histopathological feature of cerebral vascular (CV). There were significant differences in BMI, HOMA-IR, HOMA-B, and the mean number of CV (all p < 0.05) among treatment groups. E1-3 groups had a significantly lower level of blood glucose and HOMA-IR, and a higher level of HOMA-B and BMI (all p < 0.05) which tends to reduce cerebral neovascularization. HOMA-IR independently had a positive effect to induce neovascularization of CV (p < 0.05, R² = 26.8%). These findings suggested that mangosteen peel extract increased β-cell function sensitivity, and effectively suppressed insulin resistance, BMI, and cerebral neovascularization process in type 2 DM rats.

• Journal of Chest Surgery
• /
• v.39 no.8 s.265
• /
• pp.579-587
• /
• 2006

Background: Preoperative risk analysis for Fontan candidates is still less than optimal in that patients with apparently low risks may have poor surgical outcome; prolonged pleural drainage, protein losing enteropathy, pulmonary thromboembolism and death. We hypothesized that low pulmonary vascular compliance (PVC) is a risk factor for prolonged pleural effusion drainage after the Fontan operation. Material and Method: A retrospective review of 96 consecutive patients who underwent the Extracardiac Fontan procedures (median age: 3.9 years) was performed. Fontan risk score (FRS) was calculated from 12 categorized preoperative anatomic and physiologic variables. PVC $(mm^2/m^2{\cdot}mmHg)$ was defined as pulmonary artery index $(mm^2/m^2)$ divided by total pulmonary resistance $(W.U{\cdot}/m^2)$ and pulmonary blood flow $(L/min/m^2)$ based on the electrical circuit analogue of the pulmonary circulation. Chest tube indwelling time was log-transformed (log indwelling time, LIT) to fit normal distribution, and the relationship between preoperative predictors and LIT was analyzed by multiple linear regression. Result: Preoperative PVC, chest tube indwelling time and LIT ranged from 6 to 94.8 $mm^2/mmHg/m^2$ (median: 24.8), 3 to 268 days (median: 20 days), and 1.1 to 5.6 (mean: 2.9, standard deviation: 0.8), respectively. FRS, PVC, cardiopulmonary bypass time (CPB) and central venous pressure at postoperative 12 hours were correlated with LIT by univariable analyses. By multiple linear regression, PVC (p=0.0018) and CPB (p=0.0024) independently predicted LIT, explaining 21.7% of the variation. The regression equation was LIT=2.74-0.0158 PVC+0.00658 CPB. Conclusion: Low pulmonary vascular compliance is an important risk factor for prolonged pleural effusion drainage after the extracardiac Fontan procedure.

• International Journal of Vascular Biomedical Engineering
• /
• v.1 no.2
• /
• pp.4-12
• /
• 2003

The present study investigated the effect of transverse vibration on the hemorheological characteristics of blood using a newly designed pressure-scanning capillary viscometer. As vibration was applied, aggregated blood cells (rouleaux) were disaggregated. The range of vibration frequency and amplitude are $0{\sim}100\;Hz$ and $0{\sim}0.8\;mm$, respectively for a capillary diameter 0.84 mm. As vibration increased, blood viscosity initially increased and tended to decrease. In order to delineate the unexpected results, the present study proposed two counteracting mechanisms of vibration related with red blood cell (RBC) aggregation affecting hemo-rheological properties. One is the reduction of RBC aggregation due to vibration causing an increase of blood viscosity. The other is forced cell migration due to the transverse vibration, which in turn forms a cell-free layer near the tube wall and causes a decrease of flow resistance.