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  • Captopril  (5)
  • Angiotensin II  (3)
  • Springer  (8)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 64 (1986), S. 327-332 
    ISSN: 1432-1440
    Keywords: Severe hypertension ; Minoxidil ; Captopril
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The antihypertensive efficacy of minoxidil and captopril was compared in 23 males with essential or renal parenchymatous hypertension refractory to conventional antihypertensive drug therapy. Following a pretreatment period the patients were randomly assigned to receive either minoxidil, 2.5 mg twice daily (n=12), or captopril, 25 mg twice daily (n=11). In patients with diastolic blood pressure 〉95 mmHg, doses of minoxidil and captopril were increased in 2-week intervals. Patients who maintained diastolic pressure 〉95 mmHg and/or those with intolerable side effects were switched over to the alternative substance. After a mean observation period of 12 weeks a significant decrease in systolic and diastolic blood pressure was observed (179/114 vs 148/92 mmHg in the minoxidil group; 176/111 vs 158/97 mmHg in the captopril group). The primary response rate was 75% in patients treated with minoxidil and 55% in those with captopril (not significant). After the change to the alternative substance two of the four non-responders on captopril and one of the two non-responders on minoxidil became responders. Side effects occurred significantly more often during minoxidil than captopril (p〈0.05). The high efficacy of minoxidil and captopril in the treatment of severe hypertension refractory to conventional drugs was confirmed. Minoxidil lowered blood pressure slightly more than captopril, but it had a higher incidence of side effects than captopril.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 62 (1984), S. 855-858 
    ISSN: 1432-1440
    Keywords: Cushing's syndrome ; Pathogenesis of hypertension ; Renin angiotensin system ; Captopril
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To analyse the role of the renin angiotensin system in the pathogenesis of hypertension in Cushing's syndrome ten patients with hypercorticism (five with pituitary hypothalamic dysfunction, three with adrenal adenomas and two with adrenal carcinomas) received a single oral dose of 25 mg captopril. Mean arterial pressure was then determined at short intervals over periods of up to 240 min. Plasma renin activity (PRA) was measured immediately before the administration of captopril. Eleven patients with severe essential hypertension, who showed a comparable distribution of basal PRA values, served as a control. Patients with elevated basal PRA values (〉3 ng/ml·3 h) showed, both in the subgroup of cases with essential hypertension and in that with Cushing's syndrome, a statistically significant fall (P〈0.05−P〈0.001) in mean arterial pressure, the decrease being slightly more pronounced in essential hypertensives. On the other hand patients with normal PRA values (≦3 ng/ml·3 h) exhibited only a minor fall in mean arterial pressure reaching statistical significance (P〈0.05) only after 60 min (essential hypertension) and 180 min (Cushing's syndrome), respectively. Our results document that in patients with Cushing's syndrome the effect of captopril seems to be determined by the activity of the renin angiotensin system. Thus, in a substantial number of patients with hypercorticism, the renin angiotensin system may be an important factor in the pathogenesis of hypertension, whereas in patients with low PRA values other factors like oversecretion of mineralocorticoids may be responsible for the observed blood pressure increases.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 59 (1981), S. 27-34 
    ISSN: 1432-1440
    Keywords: Regulation of aldosterone ; Anephric patients ; ACTH ; Angiotensin II ; Hemodialysis ; Aldosteronregulation ; Nierenlose Patienten ; ACTH ; Angiotensin II ; Hämodialyse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 14 anephrischen Patienten wurde der Einfluß von ACTH, Angiotensin II, Orthostase und Hämodialyse auf die Plasmaaldosteronkonzentration untersucht. Gleichzeitg wurden Plasmareninaktivität (PRA), Plasmacortisol, Serumnatrium und Serumkalium bestimmt. Unter 4stündiger Infusion von synthetischem ACTH (2,5 µg/min Synachten) kam es zu einem signifikanten Anstieg des Plasmaaldosterons und des Plasmacortisols (p〈0,025 bzw. 〈0,005), während Serumnatrium und Serumkalium unverändert blieben. Eine einstündige Infusion einer suppressorischen Dosis von synthetischem Angiotensin II (1,0 ng/kg Körpergewicht/min Hypertensin) führte zu einem geringgradigen, jedoch nicht signifikanten Anstieg des Plasmaaldosterons und hatte keinen Einfluß auf Plasmacortisol und Serumelektrolyte. Eine nach 60 min zusätzlich durchgeführte ACTH-Infusion (2,5 µg/min Synacthen) bewirkte über einen Zeitraum von 4 h einen ähnlichen Plasmaaldosteronansteig wie die alleinige ACTH-Infusion. Durch Orthostase ließ sich ein signifikanter Anstieg des Plasmaaldosterons (p〈0,05) erzielen, während Plasmacortisol und Serumelektrolyte keine signifikanten Veränderungen zeigten. Sowohl normale als auch isonatriämische und isokaliämische Hämodialyse führten zu einem vergleichbaren Anstieg des Plasmaaldosterons. Das Plasmacortisol blieb bei der normalen Hämodialyse unverändert und fiel bei der isonatriämischen und isokaliämischen Hämodialyse ab. Die Plasmareninaktivität war unter den beschriebenen Versuchsbedingungen mit ganz wenigen Ausnahmen nicht meßbar (〈0,2 mg/ml·3 h). Vereinzelt tiefnormale PRA-Werte wurden weder durch Hämodialyse noch Orthostase beeinflußt. Unsere Ergebnisse zeigen bei nierenlosen Patienten eine Stimulation des Plasmaaldosterons durch synthetisches ACTH, ein geringgradiges Ansprechen auf suppressorisches Angiotensin II, eine fehlende Potenzierung der ACTH-Wirkung durch suppressorische Dosen von Angiotensin II und einen Aldosteronanstieg unter Orthostase. Ferner ließ sich unter Hämodialyse ein Anstieg des Plasmaaldosterons beobachten. Dieser Anstieg trat sowohl unter normaler als auch unter isokaliämischer und isonatriämischer Hämodialyse auf und konnte deshalb ebenso wie die durch Orthostase induzierte Veränderung der Hormonkonzentration keinem der bekannten aldosteronstimulierenden Faktoren zugeordnet werden. Eine mögliche Beteiligung anderer Faktoren an der Aldosteronregulation ist deshalb anzunehmen.
    Notes: Summary The influence of ACTH, angiotensin II, orthostasis and hemodialysis on plasma aldosterone concentration was investigated in 14 anephric patients. Furthermore, plasma renin activity (PRA), plasma cortisol, plasma sodium concentration and plasma potassium concentration were measured. After infusion of synthetic ACTH (2.5 εg/min Synacthen) for 4 h a significant rise of plasma aldosterone concentration and plasma cortisol concentration was observed (p〈0.025,p〈0.005, respectively), whereas serum sodium and serum potassium concentrations remained unchanged. A slight though not statistically significant rise of plasma aldosterone concentrations was observed after 1 h-infusion of synthetic angiotensin II (1.0 ng/kg/min Hypertensin) while plasma cortisol concentration and serum electrolytes showed only minor changes. Sixty min after starting the infusion with angiotensin II ACTH (2.5 µg/min Synacthen) was infused additionally over a period of 4 h. Under the latter conditions as with ACTH alone an increase of plasma aldosterone concentration was observed. Orthostasis caused a significant rise in plasma aldosterone (p〈0.05), whereas plasma cortisol and the serum electrolytes remained unchanged. Conventional as well as isonatriaemic and isokaliaemic hemodialysis let to a comparable increase of plasma aldosterone. Plasma cortisol was unchanged during conventional hemodialysis, and showed a decrease after isonatriaemic and isokaliaemic hemodialysis. With a few exceptions plasma renin activity (PRA) was undetectable low (〈0.2 ng/ml·3 h). In those instances where low normal PRA values were found, these values were not influenced by hemodialysis or orthostasis. Our results show that in anephric patients plasma aldosterone increased in response to synthetic ACTH, orthostasis and hemodialysis. After the infusion of angiotensin II only a slight, statistically not significant increase in plasma aldosterone concentration was observed. The simultaneous infusion of ACTH and angiotensin II let to a comparable increase in plasma aldosterone as ACTH alone. Furthermore, hemodialysis let to an increase of plasma aldosterone under conventional as well as under isokaliaemic and isonatriaemic conditions. These changes in hormone concentration as well as those induced by orthostasis could not be explained by one of the known aldosterone stimulating factors. Thus, our findings suggest that other factors may be involved in the regulation of plasma aldosterone in anephric man.
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  • 4
    ISSN: 1432-1440
    Keywords: Captopril ; Kidney function ; Essential hypertension ; Renovascular hypertension ; Renal parenchymatous hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study long-term effects of captopril on renal function in patients with various forms of severe hypertension, serum creatinine values were monitored in 76 patients under captopril therapy over a period of up to 3 years. Three different groups were formed: (1) patients with essential hypertension (n=37); (2) patients with renovascular hypertension (n=20); (3) patients with renal parenchymatous hypertension (n=19). In each of the three groups reduction in blood pressure was accompanied by increases in serum creatinine. However, both changes were more pronounced in patients with renovascular hypertension. In this group only the rise in creatinine was statistically significant and showed a slight progression with duration of captopril treatment. Group specific analysis revealed that the increase was smaller in patients with unilateral (n=16) renovascular disease than in those with bilateral (n=4) involvement, but in the former it was still significantly higher than in patients with essential or renal parenchymatous hypertension. Separation of patients according to the underlying disease of renovascular hypertension showed that renal function deteriorated less in patients with arteriosclerotic origin (n=10) than in those with fibromuscular dysplasia (n=8). Statistical evaluation of subjects with renovascular and essential hypertension still revealed significant differences in creatinine when the patients with initial plasma renin activity (PRA) below and above 6 ng/ml·3 h were compared separately. A significant correlation (r=0.73;P〈0.05) between blood pressure reduction and creatinine changes was obtained only for patients with renovascular hypertension. Finally, in all three groups of patients creatinine changes were statistically independent from daily dosages of captopril. From these data we conclude that sustained impairment of kidney function by captopril is mainly restricted to patients with renovascular hypertension and possibly results from the combined effects of low renal perfusion pressure and interference with intrarenal regulation of glomerular filtration rate by a postulated angiotensin-II-mediated mechanism.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 63 (1985), S. 361-363 
    ISSN: 1432-1440
    Keywords: Primary aldosteronism ; Captopril ; Spironolactone ; Renin-angiotensin ; Converting-enzyme ; Secondary hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In three patients with primary aldosteronism, the acute effect of a single dose of captopril on the elevated mean arterial blood pressure (MAP) was studied before and after 4 weeks of treatment with spironolactone. Before spironolactone therapy, captopril did not cause any drop in MAP. Four weeks later, after an oral daily dose of 400 mg spironolactone, MAP was still elevated in all three patients, though electrolyte abnormalities were fully corrected. Since plasma renin activity (PRA) was increased to values above the normal range, the acute effect of captopril on MAP was tested again. A single dose of 25 mg captopril then caused a fall in MAP to normal. These data reveal the conversion from a renin-independent to a renindependent kind of hypertension after spironolactone therapy in three patients with primary aldosteronism syndrome. This might be of pathogenetic and therapeutic interest.
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  • 6
    ISSN: 1432-1440
    Keywords: Angiotensin II ; Insulin ; Smooth muscle cell ; Vascular
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hypertension has a high prevalence among subjects with decreased insulin sensitivity and/or hyperinsulinemia. Furthermore, angiotensin II plays a pivotal role in the regulation of vascular tone and is known to induce hypertrophy and/or hyperplasia in vascular smooth muscle cells. In the present study, the effect of insulin on angiotensin II induced smooth muscle cell growth (Wistar-Kyoto rat) was investigated. Cell growth was assessed by the measurement of [3H]thymidine incorporation into cell DNA. Insulin in a concentration range of 1.7 × 10−10–1.7 × 10−6 M lacked any effect on cell DNA synthesis. However, insulin enhanced the angiotensin 11 induced DNA synthesis in a concentration-dependent manner. This effect was similar in cells with a weak and in cells with a marked response in DNA synthesis to stimulation with 100 nM angiotensin 11. In conclusion, insulin is able to enhance angiotensin 11 induced DNA synthesis and may therefore function as a growth cofactor in vascular smooth muscle cells.
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  • 7
    ISSN: 1432-1440
    Keywords: Angiotensin II ; Diltiazem ; Mitogenic effect ; Nifedipine ; Platelet-derived growth factor ; Vascular smooth muscle cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Structural changes within the blood vessel wall such as hyperplasia and hypertrophy of vascular smooth muscle cells are important factors in the pathogenesis of hypertension. Humoral growth factors such as angiotensin II (AII) and platelet-derived growth factor BB (PDGF-BB) may participate in the remodelling of the blood vessel wall. Whether and by which mechanisms antihypertensive treatment is capable of influencing the structural blood vessel alterations to date remains unclear. In the present study, the effect of nifedipine and diltiazem on AII- and PDGF-BB-induced vascular smooth muscle cell proliferation was examined. Nifedipine and diltiazem at a concentration of 10 μM did not affect baseline DNA synthesis in isolated vascular smooth muscle cells in culture. AII (final concentration 100 nM) and PDGF-BB (50 ng/ml) stimulated DNA synthesis by approximately 9.0- and 4.6-fold, respectively. Both AII- and PDGF-BB-induced DNA synthesis was significantly blunted by diltiazem and nifedipine in a concentration of 10 μM, while no significant influence was seen with concentrations from 10 nM up to 1 μM. In contrast, no significant influence of these drugs could be observed on fetal calf serum 5%-induced DNA synthesis. The findings indicate that calcium antagonists possess antimitogenic potential and that they may thus contribute to the regression of structural changes of the blood vessels associated with hypertension.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 59 (1981), S. 59-67 
    ISSN: 1432-1440
    Keywords: Captopril-treatment resistant hypertension ; Essential hypertension ; Renalparenchymatous hypertension ; Renovascular hypertension ; Captopril ; therapieresistente Hypertonie ; Essentielle Hypertonie ; Renalparenchymatöse Hypertonie ; Renovaskuläre Hypertonie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der vorliegenden Studie wurden 51 Patienten mit schwerer, auf eine standardisierte Dreiertherapie resistente Hypertonie (20 mit essentieller, 15 mit renovaskulärer und 16 mit renalparenchymatöser Hypertonie) mit dem oralen Converting enzyme Inhibitor Captopril behandelt. Die mittlere Behandlungszeit betrug 8,6 Monate für Patienten mit essentieller, 8,9 Monate für solche mit renovaskulärer und 9,9 Monate für Fälle mit renalparenchymatöser Hypertonie. In allen 3 Patientengruppen konnte ein ausgeprägter und anhaltender Blutdruckabfall beobachtet werden. Allerdings war sowohl der absolute Blutdruckabfall als auch die individuelle Blutdruckantwort bei Patienten mit renovaskulärer Hypertonie ausgeprägter als bei solchen mit essentieller und renalparenchymatöser Hypertonie. Diese Ergebnisse weisen damit auf einen stärkeren antihypertensiven Effekt von Captopril bei Patienten mit renovaskulärer Hypertonie hin. Unsere Resultate zeigen weiter, daß eine Monotherapie mit Captopril eher die Ausnahme als die Regel war. So benötigten über 90% der Patienten zusätzliche Gabe eines Diuretikums und ein weiterer Anteil der Patienten darüberhinaus die Gabe eines Betablockers (50% der Patienten mit essentieller, 38% der Fälle mit renalparenchymatöser und 26% der Patienten mit renovaskulärer Hypertonie). Die Plasma-Renin-Aktivität stieg unter Captoprilbehandlung erwartungsgemäß an, während die Plasma-Aldosteron-Konzentration und die Converting enzyme Aktivität abfielen. In 17,6% (n=9) der 51 Patienten konnten Nebenwirkungen (Exanthem, Pruritus, supraventrikuläre Extrasystolen, Tachykardie, Wasser- und Flüssigkeitsretention, Raynaud-Phänomen, unvollständiger und vollständiger Geschmacksverlust und Leukopenie) beobachtet werden. Unsere Ergebnisse zeigen, daß Captopril bei schwerer therapieresistenter Hypertonie ein potentes Antihypertensivum ist. Dabei war bei unseren Patienten eine Monotherapie mit Captopril eher die Ausnahme als die Regel. So benötigten die meisten Patienten zusätzlich ein Diuretikum und/oder einen Betablocker. Allerdings erfordern die Nebenwirkungen des Medikaments eine engmaschige und genaue Überwachung aller Patienten.
    Notes: Summary In this study 51 patients with severe hypertension (20 essential, 15 renovascular and 16 renalparenchymatous) resistant to a standardized triple therapy were treated with the oral converting enzyme inhibitor captopril. Mean treatment period was 8.6 in essential, 8.9 in renovascular and 9.9 months in renalparenchymatous hypertension. In each of the 3 groups a marked and sustained blood pressure reduction was observed promptly after introducing captopril. However, absolute fall in mean blood pressure as well as individual blood pressure response were more pronounced in renovascular than in essential and in renalparenchymatous hypertension demonstrating a higher blood pressure lowering activity of the converting enzyme inhibitor in the former. In addition, our results document that monotherapy with captopril was rather the exception than the rule. More than 90% of all patients required at least the addition of a diuretic and even a substantial percentage of patients needed as a third drug a betablocker (50% in essential, 38% in renalparenchymatous and 26% in renovascular hypertension). As expected renin activity increased under captopril whereas plasma aldosterone and converting enzyme activity decreased. Side-effects (skin rash, pruritus, supraventricular extrasystoles, tachycardia, water and fluid retention, Raynaud-phenomenon, incomplete and complete taste loss and leucopenia) occurred in 17.6% (n=9) of the 51 patients. Our results show that captopril is a potent blood pressure lowering agent in severe and therapy resistant hypertension. The vast majority of patients, however, required concomitant therapy with a diuretic and/or a betablocker. Finally, the frequency of drug induced side-effects necessitates a close and careful monitoring of all patients.
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