长期服用一种自由基清除剂ONO—3144对易卒中自发高血压大鼠的影响

AIM:To clarify the preventive effects of ONO-3144, a free radical scavenger, on stroke-prone spontaneously hypertensive rats (SHRSP) and free radicals related to the hypertensive disorders. METHODS: Drugs with powdered chow were administered orally to the rats from 2- to 14-month-old. Body weight, blood pressure, rectal temperature, oxygen consumption rate, thyroid hormones, lipids, platelet number, ocular fundus, autopsy, and life span were investigated. RESULTS: ONO-3144 did not affect the growth, blood pressure, concentrations of thyroid hormones and lipids in the blood, but decreased the rectal temperature and oxygen consumption rate. ONO-3144 also prevented the platelet number decrease, sclerotic change of retinal artery, edematous and hypertrophic changes in parenchymal and circulatory organs. Both the average life-span and the longest life time of SHRSP given 40 mg/kg ONO-3144 were longer than those of normotensive rats and no administration hypertensive rats. CONCLUSION: The oxidative free radic     

AT1 receptor in rostral ventrolateral medulla mediating blunted baroreceptor reflex in spontaneously hypertensive rats

AIM: To determine the role of AT1 receptor in the rostral ventrolateral medulla (RVLM) in mediating the blunted baroreceptor reflex in spontaneously hypertensive rats (SHR). METHODS: Intravenous injections of graded doses of phenylephrine (1, 5, 10, 20, and 40μg/kg) increased the blood pressure to elicit the baroreceptor reflex in both SHR and normotensive Wistar rats anesthetized with urethane. The baroreceptor reflex sensitivity (BRS) was determined before and after microinjection of Ang II, losartan, or AT1 receptor antisense oligodeoxynucleotides into the RVLM. AT1 receptor protein level in the RVLM was measured by Western blotting. RESULTS: The BRS was significantly decreased in SHR compared with normal rats. Bilateral microinjection of AT~ receptor antagonist losartan (250 nmol/h) into the RVLM partly reversed the blunted BRS in SHR, but had no significant effect on the BRS in normal rats. Ang II (1.5 nmol/h) significantly inhibited the BRS in normal rats, which was completely abolished by pretreatment with losartan. However, no significant change in the BRS was observed after microinjection of Ang Ⅱ into the RVLM in SHR. Bilateral microinjection of AT1 receptor antisense oligodeoxynucleotides (ASODN) into the RVLM partially recovered the blunted BRS in SHR after 3 h, but no significant change in the BRS was observed in normal rats. The AT1 receptor protein level significantly decreased after administration of ASODN. CONCLUSION: Blockage of AT1 receptor or inhibition of AT1 receptor protein synthesis in the RVLM enhanced the BRS in SHR, suggesting that the enhanced activities of AT1 receptor in the RVLM contribute to the blunted BRS in SHR.     

前列腺素而非一氧化氮是鳟主动脉内皮细胞舒血管因子(英文)

AIM:To identify the type of prostanoids produced by endothelial cells of trout aorta and to determine whether or not the smooth muscle responds to nitric oxide. METHODS:Ventral aortas, with and without endotheli-um from rainbow trout (S gairdneri), were incubated in a buffered salt solution. RESULTS:Addition of the calcium ionophore A23187 caused a significant increase in prostaglandin E's and a consistent increase in the stable metabolite of prostacyclin (6-keto-prostaglandin F1a) in the incubation media only when the endothelium was present. This production was inhibited by methylene blue (10umol/L). In rings of trout aorta without endothelium suspended for the measurement of isometric force in organ chambers,prostacyclin and prostaglandin E1 but not prostaglandin E2 caused concentration-dependent decreases in tension when the rings were contracted with acetyl-choline. The smooth muscle did not relax to nitric oxide but did so to sodium nitroprusside. Relaxations to the latter nitrovasodilator were no     

SHR3824, a novel selective inhibitor of renal sodium glucose cotransporter 2, exhibits antidiabetic efficacy in rodent models

Aim： The sodium glucose cotransporter 2 （SGLT2） plays an Jmportant role in renal glucose reabsorption, thus serves as a new target for the treatment of diabetes. The purpose of this study was to evaluate SHR3824 as a novel selective SGLT2 inhibitor and to characterize its in vivo effects on glucose homeostasis. The effects of chronic administration of SHR3824 on peripheral insulin sensitivity and pancreatic !5-cell function were also investigated. Methods： The in vitro potency and selectivity of SHR3824 were assessed in HEK293 cells transfected with human SGLT2 or SGLTI. Acute and multi-dose studies were performed on ICR mice, GK rats and db/db mice to assess the ability of SHR3824 to enhance urinary glucose excretion and improve blood glucose levels. 2-Deoxyglucose uptake and insulin immunohistochemical staining were performed in the soleus muscle and pancreas, respectively, of db/db mice. A selective SGLT2 inhibitor BMS512148 （dapagliflozin） was taken as positive control. Results： SHR3824 potently inhibited human SGLT2 in vitro, but exerted much weak inhibition on human SGLT1 （the IC50 values of SHR3824 against human SGLT2 and SGLT1 were 2.38 and 4324 nmol/L, respectively）. Acute oral administration of SHR3824 （0.3, 1.0, 3.0 mg/kg） dose-dependently improved glucose tolerance in ICR mice, and reduced hyperglycemia by increasing urinary glucose excretion in GK rats and db/db mice. Chronic oral administration of SHR3824 （0.3, 1.0, 3.0 mg·kg·d-1） dose-dependently reduced blood glucose and HbAlc levels in GK rats and db/db mice, and significantly increased insulin-stimulated glucose uptake in the soleus muscles and enhanced insulin staining in the islet cells of db/db mice. Conclusion： SHR3824 is a potent and selective SGLT2 inhibitor and exhibits antidiabetic efficacy in several rodent models, suggesting its potential as a new therapeutic agent for the treatment of type 2 diabetes.     

红花黄素对高血压大鼠的降压作用及对肾素-血管紧张素的影响

Safflower yellow (SY) is a mixture of chalconoid compounds extracted from Carthamus tinctorius L. Ig SY 1～2 g·kg^-1·d^-1lowered the blood pressure of spontaneously hypertensiverats (SHR), for about 1.86～3.86 kPa. Five weeks after administration of SY, the plasma renin ac-tivity and angiotensin Ⅱ level diminished in the SHR experimental groups. These suggest that the de-crease of blood pressure is mediated by the renin-angiotensin system.     

Ketanserin improves cardiac performance after myocardial infarction in spontaneously hypertensive rats partially through restoration of baroreflex function

Aim： Baroreflex dysfunction is associated with a higher rate of sudden death after myocardial infarction （MI）. Ketanserin enhances baroreflex function in rats. The present work was designed to examine whether ketanserin improves the post-MI cardiac function and to explore the possible mechanism involved. Methods： Spontaneously hypertensive rats （SHR） were treated with ketanserin （0.3 mg·k-1·d-1）. Two weeks later, blood pressure and baroreflex function were measured, followed by a ligation of the left coronary artery. The expressions of vesicular acetylcholine transporter （VAChT） and a7 nicotinic acetylcholine receptor （a7-nAChR） in ischemic myocardium, angiogenesis, cardiac function, and left ventricular （LV） remodeling were evaluated subsequently. Results： Ketanserin significantly improved baroreflex sensitivity （0.62＋0.21 vs 0.34＋0.12 ms/mmHg, P〈O.01） and vagal tonic activ- ity （heart rate changes in response to atropine, 54.8＋16.2 vs 37.6＋13.4 bpm, P〈O.01） without affecting the blood pressure or basic heart rate in SHR. Treatment of SHR with ketanserin prominently improved cardiac function and alleviated LV remodeling, as reflected by increases in the ejection fraction, fractional shortening, and LV systolic pressure as well as decreases in LV internal diameter and LV relative weight. The capillary density, vascular endothelial growth factor expression, and blood flow in the ischemic myocardium were significantly higher in the ketanserin-treated group. In addition, ketanserin markedly increased the expression of VAChT and （x7-nAChR in ischemic myocardium. Conclusion： Ketanserin improved post-MI cardiac function and angiogenesis in ischemic myocardium. The findings provide a mechanistic basis for restoring baroreflex function using ketanserin in the treatment of Ml.     

短暂脑缺血诱导成年大鼠纹状体内CRMP-4的表达

AIM: To study the expression of collapsing response mediated protein-4 (CRMP-4) and nestin in the ischemic adult rat brain following transient brain ischemia. METHODS: Brain ischemia was induced by transient left middle cerebral artery occlusion (MCAO) for 60 min in adult rats. The expression of CRMP-4, nestin and bromodeoxyuridine(BrdU) was analyzed by immunohistochemical method. The co-localization of CRMP-4 and nestin or BrdU was analyzed by double staining combined with confocal laser scanning microscopy. RESULTS: CRMP-4, a marker of immature neuron, could be expressed in the ipsilateral striatum and cerebral cortex at 1st and 2nd week after the ischemia-reperfusion; nestin, a marker of neural stem cell, occurred in above regions from several hours to 2 weeks. CRMP-4 costained with nestin and with BrdU incorporation. CONCLUSION: Neural stem cells may present in the striatum and cerebral cortex of adult rat and can be triggered to differentiate into newborn neuron there by ischemic brain trauma.     

外源性睾酮对离体家兔阴茎海绵体的影响(英文)

AIM: To study the effects of exogenous excess of testosterone on the constricting effect of phenylephrine and en-dothelium-dependent and -independent relaxing effects of different agonists in the corpus cavemosum penis (CCP). METHODS: Specimens of the CCP were obtained from rabbits testosterone for 1 and 2 months and untreated for 2 months after testosterone-treatment for 2 months. Preparations were mounted between two parallel platinum electrodes in organ baths. Responses to phenylephrine, car-bachol, and sodium nitroprusside were obtained by adding the reagent cumulatively to the bath. RESULTS: The phenylephrine-induced contractions were decreased with no change in agonist potency (pD2 value) after both 1 and 2 month testosterone-treatment and did not return to control values in corpus cavernosum obtained from rabbits untreated for 2 months after testosterone-treatment for 2 months. Testosterone treatment for 1 or 2 months increased the endothelium-dependent relaxations induced by carbachol and decrea     

食物中添加ι-卡尼汀对大鼠肝代谢ι-丙氨酸的作用(英文)

AIM:To investigate the effects of chronic supplementation with l-carnitine (LCT) on hepatic catabolism of l-alanine. METHODS: Two groups of male adult Wistar rats were used: 1) supplemented with LCT (1.2 mmol·kg-1·d-1) dissolved in the drinking water (LCT group) and 2) control group (COG) without LCT supplementation . After one week of LCT supplementation livers from 24 h-fasted rats were perfused in situ and the production of glucose, urea, pyruvate, and l-lactate from l-alanine (5 mmol/L) were measured. RESULTS: LCT decreased the production of glucose and urea from l-alanine. In agreement, pyruvate and l-lactate production from l-alanine were decreased. However, the supplementation with LCT did not show any significant effect on hepatic glucose production from pyruvate (5 mmol/L) and l-lactate (2 mmol/L). CONCLUSION: LCT supplementation decreased the conversion of l-alanine to pyruvate. However the ability of the liver to convert pyruvate to glucose was not affected by LCT treatment.     

Acetylcholine-induced endothelium-dependent contractions in the SHR aorta: the Janus face of prostacyclin

In the spontaneously hypertensive rat (SHR) and aging Wistar-Kyoto rats (WKY), acetylcholine releases an endothelium-derived contracting factor (EDCF) produced by endothelial cyclooxygenase-1, which stimulates thromboxane A2 receptors (TP receptors) on vascular smooth muscle. The purpose of the present study was to identify this EDCF by measuring changes in isometric tension and the release of various prostaglandins by acetylcholine. In isolated aortic rings of SHR, U 46619, prostaglandin (PG) H2, PGF2alpha, PGE2, PGD2, prostacyclin (PGI2) and 8-isoprostane, all activate TP receptors of the vascular smooth muscle to produce a contraction (U 46619>8-isoprostane=PGF2alpha=PGH2>PGE2=PGD2>PGI2). The contractions produced by PGH2 and PGI2 were fast and transient, mimicking endothelium-dependent contractions. PGI2 did not relax isolated aortic rings of WKY and SHR. Acetylcholine evoked the endothelium-dependent release of thromboxane A2, PGF2alpha, PGE2, PGI2 and most likely PGH2 (PGI2>PGF2alpha>or=PGE2>TXA2>8-isoprostane, PGD2). Dazoxiben abolished the production of thromboxane A2, but did not influence the endothelium-dependent contractions to acetylcholine. The release of PGI2 was significantly larger in the aorta of SHR than in WKY, and the former was more sensitive to the contractile effect of PGI2 than the latter. The inhibition of PGI-synthase was associated with an increase in PGH2 spillover and the enhancement of acetylcholine-induced endothelium-dependent contractions. Thus, in the aorta of SHR and aging WKY, the endothelium-dependent contractions elicited by acetylcholine most likely involve the release of PGI2 with a concomitant contribution of PGH2.     

Oxygen-derived free radicals mediate endothelium-dependent contractions to acetylcholine in aortas from spontaneously hypertensive rats

Experiments were designed to investigate whether or not oxygen-derived free radicals mediate endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rat (SHR). Isometric tension was measured in aortic rings taken from adult male SHR and Wistar-Kyoto rat (WKY) in the presence of NG-nitro-L-arginine. Endothelium-dependent contractions to acetylcholine were significantly greater in rings from SHR compared to WKY. Oxygen-derived free radicals, generated from xanthine plus xanthine oxidase, induced contractions that were larger in aortas from SHR than from WKY. Contractions to acetylcholine and free radicals were abolished by a selective TP-receptor antagonist, S 18886, and a preferential inhibitor of cyclo-oxygenase-1, valeryl salicylate, but not by a preferential inhibitor of cyclo-oxygenase-2, NS-398. Allopurinol, deferoxamine and the combination of superoxide dismutase plus catalase inhibited the contractions to oxygen-derived free radicals but did not significantly affect those to acetylcholine. In contrast, diethyldithiocarbamic acid, an inhibitor of superoxide dismutase, or Tiron, a scavenger of superoxide anion, reduced endothelium-dependent contractions to acetylcholine in aortas from SHR. The effect of these two drugs was additive. In SHR chronically treated with dimethylthiourea endothelium-dependent contractions to acetylcholine were decreased, and reduced further by acute in vitro exposure to deferoxamine or the combination of superoxide dismutase plus catalase. These results suggest that in the SHR aorta acetylcholine-induced endothelium-dependent contractions involve endothelial superoxide anion production and the subsequent dismutation into hydroxyl radicals and/or hydrogen peroxide. The free radicals activate cyclo-oxygenase-1, most likely to produce endoperoxides. Activation of TP-receptors is required to observe endothelium-dependent contractions to acetylcholine or endothelium-independent contractions in response to free radical generation.     

Mechanisms underlying ATP-induced endothelium-dependent contractions in the SHR aorta

In mature spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats, acetylcholine, the calcium ionophore A 23187 and ATP release endothelium-derived contracting factor (EDCF), cyclooxygenase (COX) derivatives that activate thromboxane-endoperoxide (TP) receptors on vascular smooth muscle. The EDCFs released by acetylcholine have been identified as prostacyclin and prostaglandin (PG) H(2) while in response to A 23187 thromboxane A(2), along with the two other prostaglandins, contributes to the endothelium-dependent contractions. The purpose of the present study was to identify the EDCFs produced by ATP. Isometric tension and the release of prostaglandins were measured in isolated aortic rings of WKY rats and SHR. ATP produced the endothelium-dependent release of prostacyclin, thromboxane A(2) and PGE(2) (PGI(2)>TXA(2)> or =PGE(2)>PGF(2alpha)) in a similar manner in aorta from WKY rats and SHR. In SHR aortas, the release of thromboxane A(2) was significantly larger in response to ATP than to acetylcholine while that to prostacyclin was significantly smaller. The inhibition of cyclooxygenase with indomethacin prevented the release of prostaglandins and the occurrence of endothelium-dependent contractions. The thromboxane synthase inhibitor dazoxiben selectively abolished the ATP-dependent production of thromboxane A(2) and partially inhibited the corresponding endothelium-dependent contractions. U 51605, a non-selective inhibitor of PGI-synthase, reduced the release of prostacyclin elicited by ATP but induced a parallel increase in the production of PGE(2) and PGF(2alpha), suggestive of a PGH(2)-spillover, which was associated with the enhancement of the endothelium-dependent contractions. Thus, in the aorta of SHR, endothelium-dependent contractions elicited by ATP involve the release of thromboxane A(2) and prostacyclin with a possible contribution of PGH(2).     

Differential effects of tyrosine kinase inhibitors on contraction and relaxation of the aortas of normotensive and hypertensive rats.

The contribution of tyrosine kinase activity to vasoreactivity in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats was investigated on isolated aortic preparations by the use of two tyrosine kinase inhibitors: methyl-2,5-dihydroxycinnamate (30 microM) and genistein (30 microM). The pretreatment of endothelium denuded aorta with methyl-2,5-dihydroxycinnamate reduced the sensitivity of the rings to noradrenaline to a larger extent in SHR than in WKY. The relaxing effects evoked by methyl-2,5-dihydroxycinnamate and genistein on the sustained contraction induced by endothelin-1 were also more pronounced in SHR denuded rings. Furthermore, in presence of methyl-2,5-dihydroxycinnamate, the endothelium-independent contractile responses to equipotent doses of cyclopiazonic acid were more depressed in SHR than in WKY. In WKY and SHR endothelium-intact aortas contracted with either phenylephrine or endothelin-1, carbachol and cyclopiazonic acid evoked endothelium derived relaxing factor (EDRF)/nitric oxide (NO)-dependent relaxations which were reduced by pretreatment of the rings with methyl-2,5-dihydroxycinnamate or genistein. These inhibitory effects were larger in WKY rings and more important on the cyclopiazonic acid response. In addition, sodium orthovanadate (30 microM) potentiated the noradrenaline-mediated contractions of endothelium-denuded SHR rings and reduced the cyclopiazonic acid-induced relaxation of endothelium-intact WKY rings. The present study suggests a regulatory role for tyrosine kinase in the smooth muscle contraction and the endothelium-dependent relaxation in WKY and SHR aortas and demonstrates the existence of a different relationship in the effect of tyrosine kinase inhibitors on vasoreactivity between SHR and WKY. We propose that an increase in the tyrosine kinase activity in SHR could lead to an enhanced reactivity of Ca2+-linked contractile mechanisms. In addition, our results suggest a link between the loss of tyrosine kinase activity and the altered endothelium-dependent relaxation associated with hypertension.     

Hypertension and the absence of EDHF-mediated responses favour endothelium-dependent contractions in renal arteries of the rat

Background and purpose:Experiments were designed to determine the modulation by nitric oxide (NO) and endothelium-dependent hyperpolarizations (EDHF-mediated responses) of endothelium-dependent contractions in renal arteries of normotensive and hypertensive rats.Experimental approach:Rings, with or without endothelium, of renal arteries of 8-month-old Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were suspended in myographs for isometric force recording.Key results:ACh evoked relaxations in preparations contracted with phenylephrine. L-NAME (inhibitor of NOS) attenuated (WKY) or abolished (SHR) these relaxations. TRAM-34 plus UCL 1684 (inhibitors of EDHF-mediated responses) did not decrease the relaxation, except in rings of WKY when L-NAME was also present. High concentrations of ACh caused a secondary increase in tension, augmented in rings of WKY by L-NAME or TRAM-34 plus UCL 1684. The increase in tension was prevented by indomethacin. Under baseline tension, ACh induced endothelium-dependent contractions, prevented by indomethacin (COX inhibitor) or terutroban (TP receptor antagonist). The calculated endothelium-dependent contractions were larger in rings of SHR compared with those of WKY. In preparations of SHR, the contractions were augmented by L-NAME in the presence of SC19220 (EP-1 receptor antagonist). In arteries of WKY, the endothelium-dependent contractions were augmented by TRAM-34 plus UCL 1684. The responses were reduced by SC19220.Conclusions and implications:In the renal artery of the rat, EDCF-mediated contractions are augmented by hypertension. The endothelium-dependent contractions are facilitated by NOS inhibition (in the presence of an EP-1 receptor antagonist) and by the withdrawal of EDHF-mediated responses.British Journal of Pharmacology (2008) 155, 217-226; doi:10.1038/bjp.2008.256; published online 23 June 2008.     

Mechanisms underlying biochanin A-induced relaxation of the aorta differ between normotensive and hypertensive rats

1. The aim of the present study was to investigate the mechanism underlying biochanin A-induced relaxation of the aorta in spontaneously hypertensive rats (SHR). 2. The tension in isolated ring preparations of thoracic aortas from normotensive (Wistar-Kyoto (WKY) rats) and SHR at 5 and 10 weeks of age was measured isometrically. 3. Biochanin A (10(-7) to 10(-4) mol/L) induced a concentration-dependent relaxation in aortic rings from both strains at the age of 5 and 10 weeks and the relaxation was greater in rings from 10-week-old SHR compared with age-matched WKY rats. The vasorelaxation induced by biochanin A was significantly reduced by denudation of the endothelium in aortic rings from SHR, but not WKY rats. Treatment with either indomethacin, a cyclo-oxygenase inhibitor, or N(omega)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, had little effect on the relaxation induced by biochanin A in aortic rings from either strain. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, significantly attenuated the relaxation induced by biochanin A in aortic rings from both strains, although the extent of reduction was greater in WKY rats than SHR. Conversely, treatment with 4-aminopyridine, a selective inhibitor of voltage-dependent potassium channels, or tetraethylammonium, an inhibitor of calcium-activated potassium channels, significantly reduced the vasorelaxation induced by biochanin A in rings from SHR but not WKY rats. 4. The greater vasorelaxation produced by biochanin A in aortic rings from 10-week-old SHR is endothelium dependent. Different mechanisms underlie the relaxant effects of biochanin A in aorta from SHR and WKY rats. The mechanisms of biochanin A-induced vasorelaxation in thoracic aortas from both normotensive and hypertensive rats involve ATP-sensitive potassium channels and, in addition, in rings from the hypertensive strain at 10 weeks of age, an endothelium-derived activation of smooth muscle cell potassium channels contributes to the vasorelaxation observed.     

Changes of vascular smooth muscle reactivity in hypertensive rats

Mechanical responses produced by high potassium solution (high-K), norepinephrine (noradrenaline; NA) and phenylephrine (Phe) were examined in the thoracic aorta isolated from control (WKY) and spontaneously hypertensive rats (SHR). In the SHRs the tissues showed increased sensitivity to high potassium compared with those from the control rats. Mechanical removal of endothelium in tissues from the controls did not change the response. The effects produced by NA and Phe were also increased in tissues from SHRs. The amplitudes of contractions were enhanced after removal of the endothelium in tissues from the controls. The relaxation in response to endothelium-dependent vasodilators (acetylcholine and histamine) was significantly depressed in aortic rings from SHRs. Experiments using modified sandwich preparations suggest that the defect in the relaxant ability of vascular smooth muscle is coupled to a reduced functionality of the endothelium.     

Des-aspartate angiotensin I (DAA-I) reduces endothelial dysfunction in the aorta of the spontaneously hypertensive rat through inhibition of angiotensin II-induced oxidative stress

Des-aspartate angiotensin I (DAA-I), an endogenous nonapeptide, counteracts several effects of angiotensin II on vascular tone. The aim of this study was to investigate the acute protective effect of DAA-I on endothelial function in the spontaneously hypertensive rat (SHR) as well as its effect on angiotensin II-induced contractions and oxidative stress. Aortic rings were incubated with DAA-I (0.1 μM) for 30 min prior to the assessment of angiotensin II-induced contractions (0.1 nM–10 μM) in WKY and SHR aortas. Total nitrate and nitrite levels were assessed using a colorimetric method and reactive oxygen species (ROS) were measured by dihydroethidium (DHE) fluorescence and lucigenin-enhanced chemiluminescence. The effect of DAA-I was also assessed against endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside, respectively. Angiotensin II-induced contractions were significantly reduced by DAA-I, losartan and tempol. Incubation with ODQ (soluble guanylyl cyclase inhibitor) and removal of the endothelium prevented the reduction of angiotensin II-induced contractions by DAA-I. Total nitrate and nitrite levels were increased in DAA-I, losartan and tempol treated-SHR tissues while ROS level was reduced by DAA-I and the latter inhibitors. In addition, DAA-I significantly improved the impaired acetylcholine-induced relaxation in SHR aortas whilst sodium nitroprusside-induced endothelium-independent relaxation remained unaffected. The present findings indicate that improvement of endothelial function by DAA-I in the SHR aorta is mediated through endothelium-dependent release of nitric oxide and inhibition of angiotensin II-induced oxidative stress.     

Epigallocatechin gallate elicits contractions of the isolated aorta of the aged spontaneously hypertensive rat

The present study examined the effect of the green tea catechin epigallocatechin gallate (EGCG) on endothelium-dependent responses in the aorta of 36-week-old spontaneously hypertensive rats (SHR). Isometric tension was measured in isolated aortic rings. The release of prostanoid end products was determined using enzyme immunoassay kits and the intracellular reactive oxygen species (ROS) concentration using confocal microscopy. EGCG did not improve endothelium-dependent relaxations evoked by acetylcholine, except in the presence of indomethacin. EGCG did not inhibit endothelium-dependent contractions induced by acetylcholine or ATP. At 10(-6) M and higher concentrations, EGCG caused increases in tension in the SHR aorta. The EGCG-induced contractions were accompanied by an increased production of ROS. The amount of prostanoid end products was increased significantly by EGCG, indicating that their production followed the activation of cyclooxygenase (COX). These prostanoids in turn stimulated thromboxane-prostanoid (TP) receptors and caused contractions. EGCG induced significantly smaller contractions in aortae of normotensive Wistar-Kyoto rats (WKY), accompanied with a lower production of ROS and a lesser release of prostanoids. These observations suggest that EGCG-induced contractions occur more readily in blood vessels of hypertensive than normotensive animals. The present findings indicate that the increased oxidative stress in the ageing hypertensive animals contributes to the loss of the beneficial effects and the enhancement of the adverse effects of EGCG.