共查询到20条相似文献,搜索用时 31 毫秒
1.
I. -W. Franz B. Agrawal D. Wiewel R. Ketelhut 《Journal of molecular medicine (Berlin, Germany)》1992,70(Z2):S53-S57
The present study was conducted to assess the efficacy and safety of carvedilol 50 mg as compared to metoprolol 200 mg at rest and during and after a standardized bicycle ergometric exercise test. Carvedilol is a novel non-selective -blocker without intrinsic sympathomimetic activity possessing vasodilatory properties primarily due to an 1-antagonism in the same dose range. Both drugs were effective in reducing systolic and diastolic blood pressure at rest and during and after exercise. The reduction of diastolic blood pressure was much stronger under carvedilol treatment than under metoprolol treatment at all measurement points. Carvedilol was even effective in the treatment of patients whose blood pressure was unsatisfactorily controlled by metoprolol. This shows the importance of the vasodilation component of carvedilol. No serious adverse events were observed. Carvedilol therefore promises very well as a powerful and safe drug for the treatment of essential arterial hypertension. 相似文献
2.
Arnošt Bass Karel Vondra Ratmír Rath Václav Vítek Jan Teisinger Eva Macková Štčpánka Šprynarová Marie Malkovská 《Pflügers Archiv : European journal of physiology》1976,361(2):169-173
1. | In 3 groups of men, differing as to the amount and intensity of physical training loads, increasing in the order sedentary:sporting:athletic, enzyme activities were estimated in biopsy samples of m. quadriceps femoris (vastus lateralis). The enzymes were: Hexokinase (HK), NAD: glycerol-3-phosphate dehydrogenase (GPDH), triosephosphate dehydrogenase (TPDH), lactate dehydrogenase (LDH), citrate synthase (CS), NAD: malate dehydrogenase (MDH), and 3-hydroxyacyl-CoA dehydrogenase (HOADH). Indicators of laboratory performance and whole-body metabolic capacities (maximal oxygen consumption etc.) were estimated in the sporting and athletic groups. |
2. | In the 2 latter groups, distinguished by greater physical activity, the atypical enzyme activity pattern, remarkable by a low activity of LDH and high relative activities of GPDH and HK, as reported earlier in a sedentary group (Basset al., 1975a), disappeared. The possibility of the atypical low LDH enzyme activity pattern as resulting from lack of bodily exertion is discussed. |
3. | The moderately trained sporting group distinguishes itself from the sedentary one mainly by a higher activity of LDH and by lower activities of GPDH and MDH. In the intensively trained athletic group, enzymes connected to aerobic oxidation (MDH, CS, HOADH) and GPDH also show higher activities than in the sporting group. The difference between the two more active groups is further borne out by a higher maximum oxygen uptake and carbon dioxide release of the well-trained athletic group. This difference of enzyme activity pattern may not be confined to the quadriceps femoris muscle. |
3.
The rationale for the combined use of -adrenoceptor antagonists and vasodilators is to improve the efficacy of the antihypertensive therapy and to reduce the incidence of side effects. If suitable coagents are selected and used at appropriate doses, the disadvantages of each separate component (compromised blood flow to individual organs, increase in total peripheral resistance, unfavorable lipid profile for -blockers; stimulation of counter-regulatory mechanisms, retention of water and electrolytes for vasodilators) can be balanced. In addition, the favorable effects of each (reduction in cardiovascular morbidity and mortality for -blockers, and favorable hemodynamic profile for vasodilators) may be used to advantage. Such a treatment rationale can be accomplished by a free combination or by using a dual-acting drug. From the practical point of view, the latter may be preferable. The basic requirement for such a drug is that the two effects are evoked in the same dose range. Carvedilol is a dual-acting drug designed to produce -blockade and vasodilatation in the same dose range. The vasodilatation is mediated predominantly by specific 1-adrenoceptor blockade; at markedly higher concentrations additional vasodilating actions can be observed. These effects resemble those of Ca2+ -antagonistic properties. However, they do not contribute to the acute blood-pressure-lowering activity, but may be responsible for the increased blood flow to some organs. At -blocking doses, carvedilol reduces the total peripheral resistance, and blood flow to the kidneys is preserved. Cardioprotection has been demonstrated in a variety of experimental investigations 相似文献
4.
Several studies in the past have shown the long-term beneficial effects of -blockers in congestive heart failure. Despite the interest in this mode of therapy, their clinical application has been limited due to their negative inotropic effect. A subset of the heart failure patients do not show any improvements with standard -blocker therapy. Carvedilol, a new, non-selective -blocking agent with concurrent -blocking properties, was evaluated in 17 patients with chronic heart failure secondary to ischaemic heart disease. All had resting left ventricular ejection fraction 45% and were maintained on diuretic therapy. Acute haemodynamic measurements were made after intravenous carvedilol (2.5–7.5 mg) and also after chronic therapy for 8 weeks (carvedilol 12.5–50 mg b.d.). Radionuclide ventriculography, ambulatory intra-arterial blood pressure monitoring and right heart catheterization were performed before and after 8 weeks of chronic therapy. Twelve patients completed the study and 5 were withdrawn. Symptomatic and haemodynamic improvement was demonstrated in 11 of the 12 patients after 8 weeks of therapy. Mean±standard error systolic intraarterial blood pressure (133 ± 6 to 114 ± 5 mmHg, P <0.005), heart=" rate=" (81=" ±=" 3=" to=" 61=" ±=" 1=" beats/min,=">0.005),>P <0.0001), pulmonary=" artery=" wedge=" pressure=" (19=" ±=" 2=" to=" 12=" ±=" 1=" mmhg,=">0.0001),>P <0.001) and=" systemic=" vascular=" resistance=" (1748=" ±=" 115=" to=" 1497=" ±=" 89=" dynes/=">0.001)>5/m2, P < 0.02)=" were=" reduced=" with=" an=" increase=" in=" mean=" ±=" se=" of=" stroke=" volume=" index=" (31=" ±=" 1.8=" to=" 40=" ±=" 1.6=">2/beat, P < 0.0005)=" and=" left=" ventricular=" ejection=" fraction=" (25=" ±=" 3=" %=" to=" 32=" ±=" 3=" %,=">P < 0.01)=" after=" 8=" weeks=" of=" therapy=" with=" carvedilol.=" this=" is=" in=" contrast=" to=" the=" acute=" haemodynamic=" effects=" of=" carvedilol,=" which=" only=" showed=" a=" reduction=" in=" heart=" rate=" (81=" ±=" 3=" to=" 74=" ±=" 3=" beats/min,=">P < 0.0001),=" systolic=" intra-arterial=" blood=" pressure=" (133=" ±=" 6=" to=" 117=" ±6=" mmhg,=">P < 0.0005)=" and=" pulmonary=" artery=" wedge=" pressure=" (19=" ±=" 2=" to=" 14=" ±=" 2=" mmhg,=">P < 0.002)=" at=" 10=" min=" post-injection.=" the=" systemic=" vascular=" resistance,=" left=" ventricular=" ejection=" fraction=" and=" stroke=" volume=" index=" failed=" to=" show=" any=" significant=" improvement.=" thus=" intravenous=" carvedilol=" produces=" a=" reduction=" in=" filling=" pressure,=" which=" is=" maintained=" after=" chronic=" treatment.=" this=" property=" is=" clearly=" beneficial=" for=" chronic=" heart=" failure=" patients=" and=" differs=" from=" standard=">-blockers. The discrepancy of the haemodynamic changes between the acute and chronic long-term response to carvedilol lends further support to the concept of upregulation of -adrenoceptors in cognestive heart failure. 相似文献
5.
P. Lund-Johansen P. Omvik J. E. Nordrehaug 《Journal of molecular medicine (Berlin, Germany)》1992,70(Z2):S58-S64
The cardinal hemodynamic disorder in established essential hypertension is increased total peripheral resistance. During exercise, the increase in stroke volume of the heart is abnormal. A 20-year follow-up study of the hemodynamics in essential hypertension demonstrated a progressive increase in total peripheral resistance and deterioration of the heart pump function. Long-term treatment with antihypertensive agents modifies the circulatory system in different ways. Vasodilators (angiotensin converting enzyme inhibitors, 1-blockers, and calcium antagonists) all reduce total peripheral resistance, and in general, cardiac output, heart rate, and stroke volume remain unchanged. Calcium antagonists like verapamil and diltiazem reduce the heart rate approximately 10% during exercise, but since stroke volume increases, cardiac output is unchanged. Chronic treatment with conventional -blockers induces a permanent reduction in cardiac output and heart rate during exercise. In contrast, carvedilol — a 1,2-blocker with 1-blocking activity — prevents the immediate increase in total peripheral resistance during acute -blockade. In 19 patients followed by hemodynamic measurements over 6–9 months, blood pressure was well controlled by carvedilol. During exercise, total peripheral resistance decreased 6% (P<0.05), and=" the=" reductions=" in=" heart=" rate=" and=" cardiac=" index=" were=" less=" than=" on=" conventional=">0.05),>-blockade. Echo-Doppler studies showed a significant reduction in the intraventricular septum of 13%. 相似文献
6.
H. Prast 《Inflammation research》1991,33(1-2):126-128
Young (3-week old) and adult (7-week old) spontaneously hypertensive rats (SHR) and normotensive rats (WKY) were treated with -fluoromethylhistidine (-FMH) for 29 and 13 days, respectively. Treatment of SHR and WKY with -FMH led to a pronounced decrease in the histidine decarboxylase activity and in the histamine concentration in all brain areas studied. In adult SHR, the development of hypertension was not influenced by -FMH. In young SHR, -FMH elicited a transient delay in the development of hypertension followed by a short-lasting tendency for increased blood pressure. It is concluded that histaminergic neurons of the brain play, if at all, only a secondary role in the development of hypertension in SHR.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung. 相似文献
7.
Summary The rats with chronic renal hypertension caused by constricting one renal artery, exhibit a decrease in the activity of Na–K-ATPase in the outer medulla of the untouched kidney, as compared to this activity in the kidneys of intact normotensive rats and in the untouched kidney of the rats where renal artery constriction did not result in hypertension.There were no differences between the control normotensive Wistar rats and the spontaneously hypertensive rats (SHR) in the prehypertensive and early hypertensive stages (at the age of 6–8 weeks) as far as the activities of Na–K-ATPase and oxidoreductases (SDH and LDH) in the renal cortex, the outer and inner medulla are concerned. The spontaneously hypertensive rats with chronic hypertension had at the age of 16–20 and 27–29 weeks lower activity of Na–K-ATPase, SDH, and LDH in the outer renal medulla than the control normotensive Wistar rats.The experimental results indicate that in chronic arterial hypertension there is a decrease in the activity of Na–K-ATPase, in the outer renal medulla, which suggests a reduction in the resorption capabilities of the ascending Henle's loop with respect to sodium and water. 相似文献
8.
9.
Giuseppe Cassano Bruno Stieger Heini Murer 《Pflügers Archiv : European journal of physiology》1984,400(3):309-317
The quenching of the acridine orange fluorescence was used to monitor the formation and/or dissipation of a pH in brush border vesicles isolated from rat kidney cortex or rat jejunum. Similar findings were obtained with both brush border membrane vesicle preparations.Acridine orange fluorescence was quenched by a preset pH (intravesicular acid) or by the ionophore (valinomycin/CCCP) dependent development of a pH (intravesicular acid) under conditions of potassium efflux.Under sodium efflux conditions, an acidification of the intravesicular space occurred: a) due to indirect (electrical) coupling of sodium and proton fluxes; b) due to directly coupled sodium/proton exchange.The initial rate of the dissipation of a preset pH was accelerated by pulse injections of sodium in a saturable manner; lithium partially replaced sodium. The sodium dependent acceleration in the rate of dissipation of a preset pH was not altered by replacing gluconate with chloride. Amiloride was an inhibitor of directly coupled sodium/proton exchange.An inwardly directed chloride gradient did not induce intravesicular acidification. The initial rate of the dissipative proton fluxes (preset pH) was slightly accelerated by an outwardly directed chloride gradient. Sodium/proton exchange dependent acidification of the intravesicular space was not altered by replacing gluconate with chloride.These results clearly document the existence of sodium/proton exchange in both renal and intestinal brush border membrane vesicles. In contrast, Cl/OH exchange — under our experimental conditions — must have a much smaller rate than Na/H exchange.Abbreviations HEPES
N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid
- MES
2-[N-morpholino]ethanesulfonic acid
- Tris
tris-(hydroxymethyl)aminomethane
- TMA
tetramethylammonium
- CCCP
carbonyl cyanide-m-chlorophenylhydrazone 相似文献
10.
L. A. B. Joosten M. M. A. Helsen F. A. J. van de Loo W. B. van den Berg 《Inflammation research》1994,41(Z2):C174-C176
Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis (RA). To investigate the role of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in arthritic processes we studied the effect of neutralizing antibodies against murine IL-1 and TNF in murine collagen-induced arthritis (CIA). Combined i.p. injection of anti-IL-1 and anti-IL-1 (anti-IL-1,), given before onset of the disease, completely prevented CIA. In contrast, treatment with anti-TNF at this time point only delayed the onset of arthritis. Remarkably, a single injection of anti-IL-1, was also highly effective in suppressing established arthritis, reducing both inflammation and cartilage destruction. Suppression was most pronounced with the combination of anti-IL-1 and , but anti-IL-1 alone also gave significant relief. Specific antibodies against TNF had no effect on established CIA. Of interest, anti-IL-1, treatment started after onset of CIA completely normalized chondrocyte synthetic function, which was highly suppressed in the non-treated group. It is concluded that IL-1 and TNF are important cytokines during the onset of CIA and that IL-1 is the key mediator of inflammation and cartilage damage in established CIA. 相似文献
11.
Summary A method is described for preparing the sodium salt of -oxybutyric acid from acetoacetic ester. The acetoacetic ester is reduced by aluminium amalgam in moist sulphuric acid, and the -oxybutyric acid thus obtained is then saponified to form the sodium salt of -oxybutyric acid. The yield is approximately 30%.(Presented by Active Member AMN SSSR S. E. Severin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 51, No. 6, pp. 104–105, June, 1961 相似文献
12.
13.
Bruno Hagenbuch Gertraud Stange Heini Murer 《Pflügers Archiv : European journal of physiology》1985,405(3):202-208
Basolateral membrane vesicles were isolated by a Percoll density gradient centrifugation method from small intestinal and renal proximal tubular epithelial cells. Transport of sulphate across the basolateral membrane was analyzed by measuring the uptake of tracer sulphate.In both membrane preparations, preloading the vesicles with sulphate-or hydroxyl-anions stimulated tracer sulphate uptake (trans-stimulation); an inwardly directed sodium gradient did not stimulate sulphate influx whether in the absence or in the presence of sulphate- or hydroxyl-iontrans-stimulation. Under sulphate trans-stimulation conditions, DIDS (10–4 mol/l) inhibited sulphate influx.In intestinal membranes, trans-stimulation of sulphate influx was obtained by preloading the vesicles with chloride, in renal membranes by preloading with bicarbonate. Under sulphate trans-stimulation conditions, in intestinal membranes, sulphate influx was strongly inhibited by chloride, in renal membranes, chloride inhibition was absent. Under bicarbonate trans-stimulation conditions, in renal membranes, sulphate transport was inhibited by lactate.It is concluded that small intestinal and renal proximal tubular basolateral membrane vesicles contain a transport mechanism for sulphate that cannot be energized by a sodium gradient. The transport system in small intestinal basolateral membranes seems to be different from that in renal membranes. It is suggested that the observed interaction between inorganic and organic anion transport in renal basolateral membranes is indirect.Abbreviations DIDS
4,4-Diisothiocyano-2,2-disulfonic acid stilbene
- DTT
dithiothreitol
- HEPES
N-2-hydroxyethylpiperazine-N-ethanesulfonic acid
- MES
N-morpholinoethanesulfonic acid
- PAH
p-aminohippuric acid
- PMSF
phenylmethylsulfonyl fluoride
- SITS
4-acetamido-4-isothiocyanostilbene-2,2-disulfonate
- TMA
tetramethylammonium
- Tris
tris(hydroxymethyl)aminomethane 相似文献
14.
Summary Five strains of monkey pox viruses were compared with respect to their cultural characteristics in primary and continuous cell cultures and the lesions developed in embryonated eggs and in rabbit skin as well as to their hemagglutinating activity.Four strains (Copenhagen 65-31 65-32 and 7-61) appeared to be similar in their properties. The cytopathogenic effect (CPE) was identical to that induced by vaccinia virus. There was no detectable virus multiplication in an pig kidney cell line (PEK). All four strains produced small, white, compact, hemorrhagic pock-like lesions on the chorioallantoic membrane.The strain 64–7275, isolated from healthy monkeys kidneys, had all properties of variola virus. It multiplied in the PEK cell line with a CPE. The lesions on the CAM were more compact without hemorrhage. In rabbit skin no detectable reaction occurred after infection with this strain. 相似文献
15.
The effect of brain neuronal histramine and its receptors on monoaminergic stimulation of the hypothalamic-pituitary-adrenal (HPA) activity, measured indirectly through corticosterone secretion, was investigated in conscious rats. Pretreatment with -fluoromethylhistidine, (-FMH) a histamine synthesis inhibitor, did not markedly affect the increase in serum corticosterone levels induced by intracerebroventricular (icv) injection of muscimol, a GABAA receptor agonist and noradrenaline, an - and -adrenergic agonist, and slightly diminished the corticosterone response to isoprenaline, a -adrenergic agonist. -FMH totally abolished the increase in serum corticosterone induced by carbachol, a cholinergic muscarinic receptor agonist and significantly diminished the rise in corticosterone levels induced by clonidine, an 2-adrenergic agent. Pretreatment with the histamine receptor antagonists mepyramine and cimetidine also considerably reduced the carbachol-induced corticosterone response and the response induced by clonidine.These results indicate that brain neuronal histamine is considerably involved in stimulation of the HPA axis by cholinergic muscarinic and 2-adrenergic agonists, but not by GABAA and 1- and -adrenergic agonists. 相似文献
16.
T. T. Glant M. Valyon K. Mikecz A. Cole J. J. Jacobs J. Yao K. E. Kuettner 《Inflammation research》1994,41(Z2):C172-C173
Bone resorption following either cemented or uncemented total hip replacement has been implicated as an important etiologic factor in aseptic loosening of prostheses, the most frequent cause of clinical failure. Interleukin-1 (IL-1), collagenase and prostaglandin E2 are considered to play key roles in pathological bone resorption. We have measured the actual levels and quantified the genes coding for several cytokines [IL-1, IL-1, IL-4, IL-6, platelet-derived growth factors (PDGF), transforming growth factor- (TGF) and tumor necrosis factor- (TNF)] in interfacial membranes obtained from cemented or uncemented loosened joint replacements. IL-1, IL-6 and TNF were barely detectable in the interfacial membranes either at protein or mRNA levels, while IL-1 and TGF were found to be expressed at the highest levels in freshly isolated tissues. However, the expression of IL-1 increased 10–1000-fold either in isolated cells or explant cultures of interfacial membranes within 24 h. The expression of other cytokines, measured directly in tissue or cells, did not suggest a discoordinate expression of bone-resorbing cellular mediators. 相似文献
17.
H. Makino K. Shikata T. Haramoto K. Hirata J. Wada Z. Ota T. Hayashi J. Wieslander T. Yoshida K. Yoshioka 《Virchows Archiv : an international journal of pathology》1994,424(3):235-241
The possible involvement of basement membrane-associated collagen (recognized by the monoclonal antibody JK-132) in the evolution of diabetic nephropathy was studied in kidney specimens from seven patients with noninsulin-dependent diabetes mellitus, and its distribution was compared with those of antibodies against 1 to 4 chains of type IV collagen. JK-132, a monoclonal antibody against basement membrane-associated collagen, reacted immunohistochemically exclusively with the mesangial matrix of the glomerular capillary. In contrast, antibodies to the 1 and 2 chains (IV) reacted strongly with mesangial matrix, and less strongly with the glomerular basement membrane (GBM). Antibodies to the 3 and 4 chains (IV) reacted mainly with GBM. In diabetes, JK-132 reacted most extensively with the expanded mesangial matrix, its staining intensity increasing with progression of the diabetic glomerulosclerosis. Antibodies to the 1 and 2 chains (IV) reacted prominently with the expanded mesangial matrix but less strongly with the GBM. Antibodies to the 3 and 4 chains reacted intensely with the thickened GBM. These results suggest that basement membrane-associated collagen differs from 1 to 4 chains of type IV collagen and that basement membrane-associated collagen is a good marker of mesangial expansion in diabetic nephropathy. 相似文献
18.
Chen-Hsing Hsu James M. Slavicek 《Pflügers Archiv : European journal of physiology》1982,393(4):340-343
Renal hemodynamics and renal vascular resistance (RVR) were measured in the spontaneously hypertensive rat (SHR) and in the normotensive Wistar-Kyoto rat (WKY). In addition, the autoregulatory response and segmental RVR in the SHR were studied after aortic constriction. Mean arterial pressure (MAP) and RVR were higher in the SHR than in the WKY, but renal blood flow (RBF) and glomerular filtration rate were similar in both groups. Measurement of mean afferent arteriolar diameter (AAD) by a microsphere method showed a significantly smaller AAD in SHR (17.7±0.35 m) than in the WKY (19.5±0.20 m). This decrease in AAD could account for a 47% increase in preglomerular resistance. Aortic constriction in the SHR, sufficient to reduce renal perfusion pressure from 152 to 115 mm Hg, did not alter the AAD. Since RBF and glomerular filtration were also well maintained following aortic constriction, these autoregulatory responses suggest that vessels proximal to the afferent arteriole rather than postglomerular vasculature are primarily involved in the changes on intrarenal vascular resistance in SHR. 相似文献
19.
Activated macrophages synthesize and release the potent polypeptides, interleukin-1 (IL-1) and tumor necrosis factor (TNF). In an effort to identify the cellular signals which control cytokine production by activated macrophages, we have developed anin vitro model employing the human THP-1 cell line. In the present study, THP-1 cells primed by 1.6 M phorbol 12-myristate-13-acetate (TPA) for 4 hr demonstrated a dose-and time-dependent release of IL-1 and TNF upon activation by 20 g/ml LPS. BSA/anti-BSA-coated latex beads were also a potent stimulus for IL-1 secretion. Moreover, the combination of a suboptimal concentration of LPS (200 ng/ml) plus interferon- (0.03–333 U/ml) greatly enhanced IL-1 production. Resting THP-1 monocytes not primed by TPA did not secrete IL-1 or TNF. These distinct patterns of cytokine production may be related to the developmental stages of macrophage activation. 相似文献