Joint recommendations on management of anaemia in patients with gastrointestinal bleeding in Hong Kong.

The demand for blood products continues to grow in an unsustainable manner in Hong Kong. While anaemia associated with gastrointestinal bleeding (GIB) is the leading indication for transfusion, there is no local recommendation regarding best practices for transfusion. We aimed to provide evidence-based recommendations regarding management of anaemia in patients with acute and chronic GIB. We reviewed all original papers, meta-analyses, systematic reviews, or guidelines that were available in PubMed. For acute GIB, a restrictive transfusion strategy, targeting a haemoglobin threshold of 7 to 8 g/dL, should be adopted because overtransfusion is associated with significantly higher all-cause mortality and re-bleeding. A liberal transfusion strategy should only be considered in patients with co-existing symptomatic coronary artery disease, targeting a haemoglobin threshold of 9 to 10 g/dL. When acute GIB settles, patients should be prescribed iron supplements if iron deficiency is present. For chronic GIB, iron stores should be replenished aggressively via iron supplementation before consideration of blood transfusion, except in patients with symptoms of severe anaemia. Oral iron replacement is the preferred first-line therapy, while intravenous iron is indicated for patients with inflammatory bowel disease, poor response or poor tolerability to oral iron, and in whom a rapid correction of iron deficit is preferred. Intravenous iron is underutilised and the risk of anaphylactic reaction to current preparations is extremely low. These recommendations are provided to local clinicians to facilitate judicious and appropriate use of red cell products and iron replacement therapy in patients with GIB.

A prospective randomized controlled trial evaluating the short-term outcomes of transanal hemorrhoidal dearterialization versus tissue-selecting technique.

BACKGROUND: Tissue-selecting technique (TST) is a novel stapled hemorrhoidectomy technique which targets the hemorrhoids, leaving uninvolved mucosal bridges intact and avoiding circumferential circular stapling. The aim of this study was to compare the short-term outcomes of TST and transanal hemorrhoidal dearterialization (THD). METHODS: Patients presenting with symptomatic hemorrhoids were recruited. Patients were randomized into two groups: (1) TST and (2) THD. Patient demographics, perioperative data, postoperative pain scores, recurrence and patient satisfaction scores were evaluated. Patients with acute thrombosed hemorrhoids, external hemorrhoids only, or other concomitant anal diseases were excluded. RESULTS: From January 2013 to December 2015, 80 patients were included in the study, 40 in each group. There were no significant differences between groups as regards demographic data, perioperative data and postoperative pain scores. The median symptom scores for bleeding and prolapse were significantly lower in the TST group at 1 year (bleeding 1 vs. 2, p = 0.001; prolapse 1 vs. 2, p = 0.025). There was significantly less recurrence requiring reintervention in the TST group (4/40 vs. 17/40, p = 0.001). Satisfaction was significantly greater after TST. The median satisfaction scores after TST and THD were 4 and 3 (on a scale of 1-4; 4 = excellent satisfaction) (p < 0.00001), respectively. CONCLUSIONS: Both THD and TST are safe, and they appear to have similar short-term outcomes; however, TST is associated with better improvement in symptoms, lower recurrence rates and greater patient satisfaction.

Hospital Authority audit of the outcome of endoscopic resection of superficial upper gastro-intestinal lesions in Hong Kong.

OBJECTIVES: To review the short-term outcome of endoscopic resection of superficial upper gastro-intestinal lesions in Hong Kong. DESIGN: Historical cohort study. SETTING: All Hospital Authority hospitals in Hong Kong. PATIENTS: This was a multicentre retrospective study of all patients who underwent endoscopic resection of superficial upper gastro-intestinal lesions between January 2010 and June 2013 in all government-funded hospitals in Hong Kong. MAIN OUTCOME MEASURES: Indication of the procedures, peri-procedural and procedural parameters, oncological outcomes, morbidity, and mortality. RESULTS: During the study period, 187 lesions in 168 patients were resected. Endoscopic mucosal resection was performed in 34 (18.2%) lesions and endoscopic submucosal dissection in 153 (81.8%) lesions. The mean size of the lesions was 2.6 (standard deviation, 1.8) cm. The 30-day morbidity rate was 14.4%, and perforations and severe bleeding occurred in 4.3% and 3.2% of the patients, respectively. Among patients who had dysplasia or carcinoma, R0 resection was achieved in 78% and the piecemeal resection rate was 11.8%. Lateral margin involvement was 14% and vertical margin involvement was 8%. Local recurrence occurred in 9% of patients and 15% had residual disease. The 2-year overall survival rate and disease-specific survival rate was 90.6% and 100%, respectively. CONCLUSION: Endoscopic mucosal resection and endoscopic submucosal dissection were introduced in low-to-moderate-volume hospitals with acceptable morbidity rates. The short-term survival was excellent. However, other oncological outcomes were higher than those observed in high-volume centres and more secondary procedures were required.

Characteristics of patients readmitted to intensive care unit: a nested case-control study.

OBJECTIVES: To evaluate the pattern of unplanned readmissions to the intensive care unit and identify patients at risk of readmission. DESIGN: Nested case-referent study. SETTING: Tertiary hospital, Hong Kong. PATIENTS: A total of 146 patients with unplanned intensive care unit readmission were compared with 292 control patients who were discharged from the intensive care unit alive and never readmitted. Cases and controls were matched for age, gender, and disease severity. MAIN OUTCOME MEASURES: Patient demographics, initial and pre-discharge clinical parameters, reasons for readmission, and outcomes were studied. RESULTS: During the 30-month study period, the readmission rate was 5.1%. Readmitted patients had significantly higher mortality and longer mean hospital lengths of stay (both P<0.001). Most patients in this cohort (36.3%) were readmitted for a respiratory cause. Based on classification tree analysis, postoperative patients with sepsis (adjusted P=0.043), non-operative septic patients with fluid gain 24 hours pre-discharge (adjusted P=0.013), and non-septic patients with increased sputum quantity on discharge (adjusted P=0.006) were significantly associated with intensive care unit readmission. CONCLUSION: Incomplete resolution of respiratory conditions remained an important reason for potentially preventable intensive care unit readmission. Attention to fluid balance and sputum quantity before intensive care unit discharge might prevent unplanned intensive care unit readmission.

A synopsis of current care of thalassaemia major patients in Hong Kong.

OBJECTIVE: To provide a synopsis of current thalassaemia major patient care in Hong Kong. DESIGN: Retrospective study. SETTING: All haematology units of the Hospital Authority in Hong Kong. PATIENTS: All patients with thalassaemia major with regular transfusion. RESULTS: To date, there were 363 thalassaemia major patients under the care of the Hospital Authority. Prenatal diagnosis has helped to reduce the number of indigenous new cases, but in recent years immigrant cases are appearing. The patients have a mean age of 23 (range, 1-52) years, and 78% of them are adults. In 2009, they received 18 782 units of blood. This accounted for 9.5% of all blood consumption from the Hong Kong Red Cross. In the past, cardiac iron overload was the major cause of death (65%) and few patients survived beyond the age of 45 years. The availability of cardiac iron assessment by magnetic resonance imaging (T2 MRI) to direct the use of oral deferiprone chelation has reduced the prevalence of heart failure and cardiac haemosiderosis, which should reduce mortality and improve life expectancy. CONCLUSION: The future for thalassaemia care in Hong Kong is bright. With better transfusion and chelation, it should be possible to avoid growth and endocrine deficiencies in younger patients.

A synopsis of current haemophilia care in Hong Kong.

OBJECTIVE: To provide a synopsis of current haemophilia care in Hong Kong. DESIGN: Retrospective survey. SETTING: All haematology units of the Hospital Authority in Hong Kong. PATIENTS: All patients with haemophilia A and haemophilia B. RESULTS: To date, there were 222 mild-to-severe haemophilia patients (192 type A, 30 type B) under regular public care in Hong Kong (43% were considered severe, 33% moderate, and 24% mild), which gave a crude prevalence of 6.8/100 000 male inhabitants. A total of 12.8 million units of Factor VIII and 3 million units of Factor IX were prescribed annually. This amounts to 1.83 units of FVIII per capita of the population, which is comparable to that of other developed countries. Leading causes of mortality were human immunodeficiency virus-related complications (10 cases) and cerebral bleeding (2 cases). The life expectancy of patients with severe haemophilia in Hong Kong is improving; currently the oldest patient is 60 years old. Such improved survival may be due to enhanced factor availability, prompt treatment of bleeding episodes at home, safer factor products, and better antiviral treatment. Primary prophylaxis is the accepted standard of care for severe and moderate cases, and "Factor First" has become hospital policy. However, 12 patients continue to present treatment challenges, due to the documented presence of factor inhibitors. In all, 28, 100, and 14 cases respectively were positive for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus; the youngest patients with the corresponding infections being 28, 13, and 22 years old. Comprehensive care with dedicated physiotherapy, surgical support, and radionucleotide synovectomy may reduce morbidity further. CONCLUSION: A multidisciplinary approach can further improve the future care for haemophilia patients in Hong Kong.

Rosuvastatin improves endothelial function in db/db mice: role of angiotensin II type 1 receptors and oxidative stress.

BACKGROUND AND PURPOSE: HMG-CoA reductase inhibitors, statins, with lipid-reducing properties combat against atherosclerosis and diabetes. The favourable modulation of endothelial function may play a significant role in this effect. The present study aimed to investigate the cellular mechanisms responsible for the therapeutic benefits of rosuvastatin in ameliorating diabetes-associated endothelial dysfunction. EXPERIMENTAL APPROACH: Twelve-week-old db/db diabetic mice were treated with rosuvastatin at 20 mg·kg⁻¹ ·day⁻¹ p.o.for 6 weeks. Isometric force was measured in isolated aortae and renal arteries. Protein expressions including angiotensin II type 1 receptor (AT1R), NOX4, p22(phox) , p67(phox) , Rac-1, nitrotyrosine, phospho-ERK1/2 and phospho-p38 were determined by Western blotting, while reactive oxygen species (ROS) accumulation in the vascular wall was evaluated by dihydroethidium fluorescence and lucigenin assay. KEY RESULTS: Rosuvastatin treatment of db/db mice reversed the impaired ACh-induced endothelium-dependent dilatations in both renal arteries and aortae and prevented the exaggerated contractions to angiotensin II and phenylephrine in db/db mouse renal arteries and aortae. Rosuvastatin reduced the elevated expressions of AT1R, p22(phox) and p67(phox) , NOX4, Rac1, nitrotyrosine and phosphorylation of ERK1/2 and p38 MAPK and inhibited ROS production in aortae from db/db mice. CONCLUSIONS AND IMPLICATIONS: The vasoprotective effects of rosuvastatin are attributed to an increase in NO bioavailability, which is probably achieved by its inhibition of ROS production from the AT1R-NAD(P)H oxidase cascade.

Raloxifene protects endothelial cell function against oxidative stress.

BACKGROUND AND PURPOSE: Maintaining a delicate balance between the generation of nitric oxide (NO) and removal of reactive oxygen species (ROS) within the vascular wall is crucial to the physiological regulation of vascular tone. Increased production of ROS reduces the effect and/or bioavailability of NO, leading to an impaired endothelial function. This study tested the hypothesis that raloxifene, a selective oestrogen receptor modulator, can prevent endothelial dysfunction under oxidative stress. EXPERIMENTAL APPROACH: Changes in isometric tension were measured in rat aortic rings. The content of cyclic GMP in aortic tissue was determined by radioimmunoassay. Phosphorylation of endothelial NOS (eNOS) and Akt was assayed by Western blot analysis. KEY RESULTS: In rings with endothelium, ACh-induced relaxations were attenuated by a ROS-generating reaction (hypoxanthine plus xanthine oxidase, HXXO). The impaired relaxations were ameliorated by acute treatment with raloxifene. HXXO suppressed the ACh-stimulated increase in cyclic GMP levels; this effect was antagonized by raloxifene. The improved endothelial function by raloxifene was abolished by ICI 182,780, and by wortmannin or LY294002. Raloxifene also protected endothelial cell function against H2O2. Raloxifene increased the phosphorylation of eNOS at Ser-1177 and Akt at Ser-473; this effect was blocked by ICI 182,780. Finally, raloxifene was not directly involved in scavenging ROS, and neither inhibited the activity of xanthine oxidase nor stimulated that of superoxide dismutase. CONCLUSION AND IMPLICATIONS: Raloxifene is effective against oxidative stress-induced endothelial dysfunction in vitro through an ICI 182,780-sensitive mechanism that involves the increased phosphorylation and activity of Akt and eNOS in rat aortae.

Effects of meals with high soluble fibre, high amylose barley variant on glucose, insulin, satiety and thermic effect of food in healthy lean women.

OBJECTIVE: To examine the effect of barley flour (barley cultivar, Hordeum Vulgare var Himalaya 292) incorporated into breakfast and lunch compared with otherwise identical meals containing white wheat flour on the thermic effect of food (TEF), subsequent food intake and metabolic parameters. DESIGN: Randomized single blinded crossover study. SETTING: Outpatient setting. SUBJECTS AND METHODS: Fourteen healthy women consumed a test breakfast at 0700 h. Energy expenditure, respiratory quotient (RQ), appetite ratings using a visual analogue scale (VAS), insulin and glucose levels were measured before and after a test lunch at 1330 h. Food intake was recorded for the remainder of the day. RESULTS: The TEF was 5% for both test lunches and meal type did not affect any variable measured by the VAS. There was an increase in post-prandial RQ above baseline (0.80) independent of treatment (0.88 and 0.90 for barley and wheat-containing meals, respectively, P<0.001). Mean area under the glycaemic response curve (AUC) for wheat-containing meals was 4.68+/-1.67 mmol/l/h, 22% higher than for the barley-containing meals (3.67+/-1.91 mmol/l/h), P=0.05. AUC of insulin in response to wheat-containing meals (78.1+/-35.3 mIU/l/h) was 32% greater than barley-containing meals (52.8+/-24.7 mU/l/h), P<0.02. Ad libitum food intake over the next 10 h was reduced by 23% (9.6 vs 11.0 MJ, P<0.05) after the wheat-containing meals compared to the barley-containing glycaemic index meals. CONCLUSION: Inclusion of an ingredient containing increased soluble fibre and amylose did not reduce spontaneous food intake but rather was associated with higher subsequent energy intakes despite its reduced glycaemic and insulinemic effects. SPONSORSHIP: CSIRO, Human Nutrition, Adelaide, Australia.

The relaxant effect of urocortin in rat pulmonary arteries.

Urocortin is a potent vasodilator, which plays physiological or pathophysiological roles in systemic circulation. However, little is known about its action on pulmonary circulation. The present study was aimed to characterize some cellular mechanisms underlying the relaxant effect of urocortin in isolated rat pulmonary arteries. Changes in isometric tension were measured on small vessel myographs. Urocortin inhibited U46619-induced contraction with reduction of the maximal response. Urocortin-induced relaxation was independent of the presence of endothelium. Inhibitors of nitric oxide (NO)-dependent dilator, NG-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one, did not affect the relaxation. Astressin (100-500 nM), a corticotropin-releasing factor (CRF) receptor antagonist and KT5720, a protein kinase A (PKA) inhibitor reduced urocortin-induced relaxation. Urocortin produced less relaxant effect in 30 mM K+- than U46619-contracted arterial rings. Urocortin did not reduce CaCl2-induced contraction in 60 mM K+-containing solution. Ba2+ (100-500 microM) but not other K+ channel blockers reduced the relaxant responses to urocortin. Urocortin also relaxed the rings preconstricted by phorbol 12,13-diacetae in normal Krebs solution while this relaxation was less in a Ca2+-free solution. Our results show that urocortin relaxed rat pulmonary arteries via CRF receptor-mediated and PKA-dependent but endothelium/NO or voltage-gated Ca2+ channel-independent mechanisms. Stimulation of Ba2+-sensitive K+ channel may contribute to urocortin-induced relaxation. Finally, urocortin relaxed pulmonary arteries partly via inhibition of a PKC-dependent contractile mechanism.

Preliminary results of using a commercial fibrin sealant in the treatment of fistula-in-ano.

A prospective non-randomised study fibrin sealant injection to manage patients with fistula-in-ano, with magnetic resonance imaging (MRI) monitoring, was performed during the period 5/6/1999 to 28/2/2000. The aim was to determine whether a fibrin sealant could be used as a treatment modality for anorectal fistula and the usefulness of MRI perineum to monitor the disease activity. Ten patients were included in the study. Mean age was 47 years (range 7 months to 70 years). Male: female ratio was 9:1. Mean follow-up duration was 26.4 weeks. The overall success rate was 60%. The success rate of different fistula types were different (60%, 0%, 100% for intersphincteric, transphincteric, subcutaneous, respectively). Variable decrease in signal on STIR images and contrast enhancement was noted in the patients with successful and failure of fibrin sealant injection. In conclusion, fibrin sealant injection is a useful alternative treatment in the management of fistula-in-ano. MRI is helpful in delineating the anatomy of fistula-in-ano but not a useful tool to follow-up disease activity.

Stimulation of chloride secretion by baicalein in isolated rat distal colon.

The effect of baicalein on mucosal ion transport in the rat distal colon was investigated in Ussing chambers. Mucosal addition of baicalein (1-100 microM) elicited a concentration-dependent short-circuit current (I(sc)) response. The increase in I(sc) was mainly due to Cl(-) secretion. The presence of mucosal indomethacin (10 microM) significantly reduced both the basal and subsequent baicalein-evoked I(sc) responses. The baicalein-induced I(sc) were inhibited by mucosal application of diphenylamine-2-carboxylic acid (100 microM) and glibenclamide (500 microM) and basolateral application of chromanol 293B (30 microM), a blocker of K(v)LQT1 channels and Ba(2+) ions (5 mM). Treatment of the colonic mucosa with baicalein elicited a threefold increase in cAMP production. Pretreating the colonic mucosa with carbachol (100 microM, serosal) but not thapsigargin (1 microM, both sides) abolished the baicalein-induced I(sc). Addition of baicalein subsequent to forskolin induced a further increase in I(sc). These results indicate that the baicalein evoked Cl(-) secretion across rat colonic mucosa, possibly via a cAMP-dependent pathway. However, the action of baicalein cannot be solely explained by its cAMP-elevating effect. Baicalein may stimulate Cl(-) secretion via a cAMP-independent pathway or have a direct effect on cystic fibrosis transmembrane conductance regulator.

Different role of endothelium/nitric oxide in 17beta-estradiol- and progesterone-induced relaxation in rat arteries.

The present study was aimed to examine the different role of endothelium/nitric oxide in relaxation induced by two female sex hormones, 17beta-estradiol and progesterone in rat isolated aortas and mesenteric arteries. The isometric force of each ring was measured with Grass force-displacement transducers in the organ bathes. 17beta-Estradiol induced both endothelium-dependent and -independent relaxation in the rat aortas but only the endothelium-independent relaxation in the rat mesenteric arteries. In contrast. progesterone induced both endothelium-dependent and -independent relaxation in the rat mesenteric arteries but only endothelium-independent relaxation in rat aortas. N(G)-Nitro-L-arginine methyl ester and methylene blue attenuated the relaxant response to 17beta-estradiol in the aortic rings or to progesterone in the mesenteric arteries. Pretreatment with L-arginine antagonized the effect of N(G)-nitro-L-arginine methyl ester on sex hormone-induced relaxation. The endothelium contribution to relaxation seems to only relate to lower concentrations of 17beta-estradiol and progesterone. In summary, the present results clearly demonstrate a different role of the functional endothelium in the relaxant response to 17beta-estradiol or progesterone in the conduit vessel (aorta) and the resistance vessels (mesenteric artery). Nitric oxide contributes largely to the endothelium-dependent relaxation induced by 17beta-estradiol in the isolated aortas or by progesterone in the mesenteric arteries.

Inhibitory effect of tetrabutylammonium ions on endothelium/nitric oxide-mediated vasorelaxation.

Apart from the well-described K+ channel blocking effects in vascular smooth muscle cells, monovalent quaternary ammonium ions may also interact with endothelial cells in the endothelium-intact mammalian arteries. The present study was aimed to examine the effect of tetrabutylammonium ions on endothelium-dependent and -independent relaxation in the rat isolated aortic rings. Pretreatment with tetrabutylammonium concentration dependently reduced the endothelium-dependent relaxation induced by acetylcholine, cyclopiazonic acid and ionomycin. Tetrabutylammonium also inhibited endothelium-independent relaxation induced by hydroxylamine or nitroprusside. Pretreatment of endothelium-denuded rings with tetrabutylammonium did not affect relaxation induced by NS1619 or by diltiazem. In contrast, tetrabutylammonium significantly reduced the pinacidil- or cromakalim-induced relaxation. Tetrabutylammonium also inhibited the acetylcholine- but not nitroprusside-induced increase of tissue content of cyclic GMP in the aortic rings. The present study indicates that tetrabutylammonium ions could inhibit endothelial and exogenous nitric oxide-mediated aortic relaxation while it had no effect on relaxation induced by activation of Ca2+-activated K+ channels (by NS1619) or by inhibition of voltage-gated Ca2+ channels (by diltiazem). The inhibitory effect on pinacidil- and cromakalim-induced relaxation suggests that tetrabutylammonium ions also inhibit ATP-sensitive K+ channels in aortic smooth muscle cells.

Cardiovascular actions of berberine.

Berberine, is an alkaloid from Hydrastis canadensis L., Chinese herb Huanglian, and many other plants. It is widely used in traditional Chinese medicine as an antimicrobial in the treatment of dysentery and infectious diarrhea. This manuscript describes cardiovascular effects of berberine and its derivatives, tetrahydroberberine and 8-oxoberberine. Berberine has positive inotropic, negative chronotropic, antiarrhythmic, and vasodilator properties. Both derivatives of berberine have antiarrhythmic activity. Some cardiovascular effects of berberine and its derivatives are attributed to the blockade of K+ channels (delayed rectifier and K(ATP)) and stimulation of Na+ -Ca(2+) exchanger. Berberine has been shown to prolong the duration of ventricular action potential. Its vasodilator activity has been attributed to multiple cellular mechanisms. The cardiovascular effects of berberine suggest its possible clinical usefulness in the treatment of arrhythmias and/or heart failure.

Purification of phenylethanoids from Brandisia hancei and the antiproliferative effects on aortic smooth muscle.

The present study describes the isolation and purification of acteoside, 2'-acetylacteoside, poliumoside and brandioside, four phenylethanoid glycosides from Brandisia hancei. We examined their effects on the proliferation of cultured A7r5 rat aortic smooth muscle cells. The proliferative response was measured from the [(3)H]-thymidine incorporation into DNA. All four glycosides suppressed the proliferative response in the presence of 2 % or 5 % fetal bovine serum in a concentration-dependent manner. The rank order of effectiveness for inhibition of cell proliferation was: brandioside > or = poliumoside > 2'-acetylacteoside > or = acteoside. The acetyl group at position 2' of glucose does not seem necessary for the anti-proliferative effects of acteoside and 2'-acetylacteoside, while the hydroxy groups of the aromatic rings appear to play a role. Inhibition of smooth muscle cell proliferation by phenylethanoids indicates that these compounds may have preventative effects on arteriosclerosis.

Relaxing effects of Ligstrum purpurascens extract and purified acteoside in rat aortic rings.

The present study describes the effects of an extract obtained from the leaves of Ligstrum purpurascens and acteoside purified from the extract on the contractile response to various agonists in rat isolated aortic rings. L. purpurascens extract relaxed 9,11-dideoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F2 alpha (U46619)-preconstricted rings in a concentration-dependent manner (IC50: 0.14 +/- 0.01 mg/ml with endothelium and 0.16 +/- 0.01 mg/ml without endothelium). The extract also reduced contraction induced by 35 mM K+ or by 1 microM phorbol 12,13-diacetate (PDA) in endothelium-intact rings. The extract (0.1-0.3 mg/ml) reduced the concentration-response to U46619 in normal Krebs solution or to CaCl2 in 35 mM K(+)-containing solution. Acteoside accounts for 2.05% of total L. purpurascens extract in weight. Acteoside induced relaxation of rings preconstricted by U46619 (IC50: 0.22 +/- 0.01 mg/ml) but it caused an increase in 35 mM K(+)-induced tone. Removal of endothelium enhanced the relaxing effect of acteoside. Besides, pretreatment with acteoside inhibited endothelium/nitric oxide-mediated relaxation induced by acetylcholine. These results indicate that acteoside is unlikely the major ingredient responsible for the vasodilator effect of L. purpurascens extract. The extract relaxed the preconstricted aortic rings probably through multiple mechanisms by acting on smooth muscle cells. The inhibitory effect on endothelial nitric oxide-mediated relaxation suggests that acteoside could also act on the endothelial cells to reduce nitric oxide release.

Vasorelaxant effects of cardamonin and alpinetin from Alpinia henryi K. Schum.

The vascular effects of cardamonin and alpinetin from Alpinia henryi K. Schum. were examined in the rat isolated mesenteric arteries. 1H and 13C nuclear magnetic resonance spectra showed that cardamonin is present in trans-form, and single-crystal radiographic structure revealed that alpinetin is present in S configuration. Both cardamonin and alpinetin produced a rightward shift in the concentration-response curve for phenylephrine in a noncompetitive manner, and they induced relaxation of phenylephrine-preconstricted arteries with respective mean inhibitory concentrations (IC50) of 9.3+/-0.6 microM and 27.5+/-2.8 microM. Both compounds also relaxed arteries preconstricted by endothelin I or U46619. Their relaxant effects were decreased in endothelium-removed rings. Pretreatment with N(G)-nitro-L-arginine methyl ester or methylene blue inhibited relaxation induced by both agents, and pretreatment with L-arginine reversed the effect of N(G)-nitro-L-arginine methyl ester on cardamonin-induced endothelium-dependent relaxation. The relaxant effects of cardamonin and alpinetin were unaffected by indomethacin (3 microM). Cardamonin and alpinetin inhibited 60 mM K+-induced contraction with respective IC50 of 11.5+/-0.3 microM and 37.9+/-3.6 microM. In addition, both agents inhibited the transient contraction induced by 3 microM phenylephrine or by 10 mM caffeine in Ca2+-free Krebs solution. Finally, these two agents also concentration dependently relax the arteries preconstricted by 1 microM phorbol 12,13-diacetate in Ca2+-free Krebs solution. These results indicate that purified cardamonin and alpinetin from A. henryi K. Schum. relaxed rat mesenteric arteries through multiple mechanisms. They induced both endothelium-dependent and -independent relaxation; the former is likely mediated by nitric oxide whereas the latter is probably mediated through nonselective inhibition of Ca2+ influx and intracellular Ca2+ release and inhibition of the protein kinase C-dependent contractile mechanism.