摘要:

SUMMARY1. Transforming growth factors‐β (TGF‐β) are multifunctional proteins that regulate cell growth, differentiation, migration and extracellular matrix production and have an important role in embryonic development and tissue remodelling.2. The diverse biological actions of TGF‐β are elicited following their interaction with type I and type II TGF‐β receptors, both of which are transmembrane serine/threonine kinases, suggesting an important role for protein phosphorylation in the mechanism of action of these cytokines on the growth of cells and their extracellular environment.3. Alterations in TGF‐β gene expression and action in various cell types associated with the cardiovascular system may contribute to the pathophysiology of a number of diseases, such as hypertension, atherosclerosis and restenosis, as well as the development of cardiac

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02595.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. There is increasing evidence that sulfonylurea and biguanide oral hypoglycaemic drugs have cardiovascular effects and influence risk factors for cardiovascular disease in patients with non‐insulin‐dependent diabetes because of actions that are unrelated to alterations in glycaemic control.2. While sulfonylureas may have anti‐arrhythmic effects following myocardial ischaemia, there is concern that their action on vascular ATP‐sensitive potassium channels may contribute to elevated blood pressure and enhanced vascular responsiveness.3. In contrast to sulfonylureas, metformin (a biguanide) appears to reduce blood pressure and have beneficial effects on plasma lipoproteins by reducing low‐density lipoprotein cholesterol and possibly increasing high‐density lipoprotein cholesterol levels.4. The pharmacological basis and clinical significance of these effects of sulfonylureas and biguanides require further in

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02596.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. The effects of DC‐015, a newly synthesized quinazoline derivative, on plasma lipids, lipoprotein levels and vascular reactivity were investigated in Wistar‐Kyoto rats (WKY) and spontaneously hypertensive rats (SHR).2. The hypotensive effect of DC‐015 was compared with prazosin in SHR. Intravenous administration of DC‐015 and prazosin (both at 0.01, 0.05 and 0.1mg/kg) induced dose‐dependent reductions in mean arterial pressure (MAP) which reached a maximal effect 5 min after injection and persisted over 2 h in SHR. DC‐015 decreased MAP with equal efficiency compared with prazosin.3. The plasma levels of total cholesterol (CE), low‐density lipoprotein (LDL)‐CE and total triglyceride (TG) were markedly increased and the levels of high‐density lipoprotein (HDL)‐CE were markedly decreased in both high fat‐high cholesterol (HF‐HC) diet fed WKY and SHR.4. In HF‐HC diet fed WKY and SHR, the total plasma CE, LDL‐CE and total plasma TG were significantly reduced after oral administration of DC‐015 (1 mg/kg, twice a day) for 4 weeks. Furthermore, DC‐015 therapy was associated with increased HDL‐CE levels and thus the ratio of total CE to HDL‐CE was improved. The antihyperlipidaemic effect of prazosin was less than that of DC‐015.5. Significantly attenuated median effective concentration (EC50) values and augmented maximal responses for phenyl‐ephrine‐induced contraction of aortic rings were observed in HF‐HC diet fed WKY and SHR. Endothelium‐dependent relaxation to acetylcholine was impaired while endothelium‐independent relaxation to nitroglycerin was well preserved.6. Oral administration of DC‐015 (1 mg/kg, twice a day) for 4 weeks significantly augmented EC50values and attenuated maximal responses for phenylephrine‐induced contraction of aortic rings in HF‐HC diet fed WKY and SHR. Prazosin (1 mg/kg, twice a day) showed a lesser extent of efficiency than DC‐015 at normalization of vasorelaxation in HF‐HC diet fed WKY and SHR.7. It is concluded that DC‐015, a potent antihypertensive agent, may

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02597.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. Aqueous celery extract was administered intraperitoneally to genetically hypercholesterolaemic (RICO) and normochol‐esterolaemic (RAIF) rats via Alzet osmotic pumps over a 13 day period.2. The serum cholesterol concentration of the celery extract‐treated RICO rats was found to be significantly lower (P<0.05) than the control rats. Aqueous celery extract was effective in preventing the rise of cholesterol level in the RICO rats. However, no such observation was seen in the RAIF rats. The serum triglyceride level was unchanged in both strains of rats.3. When 3‐n‐butylphthalide (BuPh), a unique component in celery, was administered in the same manner to the RICO and RAIF rats, it did not produce significant changes in the serum and liver lipid profiles of these rats. The activities of hepatic 3‐hydroxy‐3‐methylglutaryl CoA reductase in both strains of rats were also not significantly different from their respective controls.4. Together with our recently reported thin‐layer chroma‐tography findings that BuPh was not detected in the aqueous celery extract, this study suggests that the effect of celery extract on serum cholesterol levels in the RICO rats could be attributed to chemical constituent

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02598.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. We have previously described an increased sensitivity to inhibition by nifedipine of noradrenaline‐induced contractures of blood vessels in hypertension. In this study we have investigated whether changes in blood pressure (BP) change the sensitivity to nifedipine and K+of aortic rings from normotensive (Wistar‐Kyoto rats, WKY) and stroke‐prone spontaneously hypertensive rats (SHRSP).2. SHRSP were treated with: hydralazine plus hydrochloro‐thiazide; captopril plus hydrochlorothiazide; hydralazine plus guanethidine; or captopril alone. WKY rats were treated with deoxycorticosterone acetate (DOCA) and NaCl. Treatment commenced from 5 weeks of age and continued until 13–15 weeks.3. The SHRSP treatments produced similar reductions in BP, and the BP of all the treated groups were significantly lower than the mean BP of untreated SHRSP (201.0 ± 7.7 mmHg). The mean BP of the treated WKY rats (134.2 ± 7.6 mmHg) was significantly higher than the mean BP of the untreated WKY rats (86.8 ± 7.4 mmHg).4. An area‐under‐curve (AUC) analysis of the inhibitory effects of nifedipine on responses of aortae to noradrenaline showed no differences between treated and untreated SHRSP groups (overall mean 40.6 ± 1.9% and 43.4 ± 3.4% inhibition of control AUC, respectively), or between DOCA‐salt treated WKY and untreated WKY groups (58.8 ± 5.9 and 64.8 ± 2.3, respectively). Noradrenaline‐induced contractures of aortae from all SHRSP groups were significantly more sensitive to inhibition by nifedipine than aortae from both WKY groups.5. The molar concentration of agonist required to evoke 50% of the maximum response (EC50) values for potassium chloride (KCI) were significantly increased in the aortae of all treated SHRSP groups in comparison to those from untreated SHRSP (treated SHRSP groups, 15.53 ± 0.68 mmol/Lvsuntreated SHRSP group, 11.36 ± 1.10 mmol/L). The EC50values for KC1 for the aortae from the DOCA‐treated WKY rats were significantly less than those from aortae of the untreated WKY (11.80 ± 0.80 and 17.08 ± 1.50 mmol/L, respectively).6. We conclude that reduction (in SHRSP) or increase (in WKY) of the BP has no effect on the sensitivity of aortic smooth muscle to the inhibitory effects of nifedipine on responses to noradrenaline, suggesting that alterations in voltage‐dependent Ca2+mechanisms may be a primary phenomenon in the SHRSP. In contrast, the fact that sensitivity to KC1 changes in the treated SHRSP and WKY aortae suggests such sensitivity is secondary to the BP and thus a separate phenomenon from

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02599.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. It has been reported that free radicals prevent wound healing. However, the mechanism of this effect is not yet clear. We attempted to clarify the influence of hydroxyl radicals on wound healingin vitro.2. We used an ascorbate‐copper ion system (ACS) to produce hydroxyl radicals in accordance with variables of time elapsed and concentration of copper ion. The effects of hydroxyl radical on fibroblast‐mediated collagen remodelling, cell viability, the functions of fibroblasts and collagen fibrils were studied.3. With a copper ion concentration of 100μmol/L ACS significantly reduced contraction, while 10μmol/L stimulated contraction. Hydrogen peroxide (H2O2) was employed in observing these findings. ACS did not influence cell viability, the expression of α2β1integrin and cellular fibronectin, or the cytoskeletal organization of fibroblasts involving actin until 3h. A concentration of ACS at 10μmol/L of copper ion induced the polymerization of collagen after 30 min, while ACS at 100 μmol/L induced collagen degradation; this finding was also established by using H2O2. Collagen reduced the amount of formaldehyde produced by trapping hydroxyl radical with dimethyl sulfoxide.4. Our findings suggest that collagen is denatured by scavenging the hydroxyl radical before fibroblasts are damaged, so that the radical may influence the remodelling of

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02600.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. A comparison was made on the protective effects of the following: ME3221, a competitive angiotensin AT1receptor antagonist; losartan, in which a major active metabolite is a non‐competitive angiotensin AT1receptor antagonist; and enalapril, an angiotensin‐converting enzyme inhibitor, using the salt‐loaded stroke‐prone spontaneously hypertensive rats (SHRSP).2. SHRSP received orally ME3221 (3 and 10mg/kg per day), losartan (10mg/kg per day) and enalapril (10mg/kg per day) from the 6th to the 20th week of age. All the control rats showed rapid elevation of systolic blood pressure (SBP), accompanied by hypertensive complications, and died by 15 weeks of age.3. ME3221, losartan and enalapril suppressed the elevation of SBP in the salt‐loaded SHRSP to a comparable degree. ME3221 and losartan increased the survival rate to>90%, and diminished hypertensive complications such as cerebral apoplexy (stroke), renal injury (increased proteinuria, and totalN‐acetyl‐β‐D‐glucosaminidase activity) and heart failure (cardiac hypertrophy and pleural effusion).4. Competitive (ME3221) and non‐competitive (losartan) angiotensin AT1receptor antagonists showed comparable efficacy against the complications and mortality of the salt‐loaded SHRSP; both were more potent than enalapril in

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02601.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. The effects of a formula of traditional Chinese medicine, TBL‐1, on collagen‐induced arthritis (CIA) were investigated in DBA/1J mice.2. From 4 weeks after the first immunization with bovine type II collagen (CII), TBL‐1 or indomethacin was administered orally for 13 weeks.3. Clinical scores of CIA were decreased by both TBL‐1 and indomethacin intervention compared with the control CII‐immunized group.4. Radiographic scores of phalangeal destruction were markedly improved by TBL‐1 intervention (P<0.001), but indomethacin failed.5. The suppressive effects of TBL‐1, but not indomethacin, were manifested in reduced serum anti‐CII antibody titres (P<0.001).6. These findings suggest that TBL‐1 may play a role in regulating some immune responses in the presen

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02602.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY1. High potassium (K) diets are known to prevent hypertensive arterial lesions and reduce stroke incidence without affecting blood pressure.2. To elucidate the mechanism of this beneficial effect, we studied the effect of K supplementation on the extravasation of plasma albumin in high NaCl‐fed stroke‐prone spontaneously hypertensive rats (SHRSP). Increased permeability of the endo‐thelium to macromolecules is assumed to be an early manifestation of vascular injury.3. The disappearance of intravenously injected [125I]‐albumin was examined in SHRSP rats fed high NaCl diets containing either 0.5% normal K or 2.1% high K for 5 weeks.4. The bodyweight, blood pressure, plasma volume and urinary protein excretion were not significantly different between the two SHRSP groups.5. The high K SHRSP showed a slower plasma albumin disappearance rate than the normal K SHRSP (10.3 vs 14.7%/h,P<0.004). The albumin radioactivity remaining in the aortic wall and in the brain after removing blood after perfusion was lower in the high K SHRSP than in the normal K SHRSP (aorta, ‐ 20%,P<0.02; brain, ‐ 26%,P<0.04).6. These results suggest that the high K diet reduced the endothelial permeability to albumin in high NaCl‐fed SHRSP rats. High K diets may have a protective effect against endothelial dysfunction and thereby contribute to the reduction of vascular lesion formation and str

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02603.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1996.tb02604.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY