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  • Captopril  (5)
  • phospholamban  (4)
  • Springer  (9)
  • 1
    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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  • 2
    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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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 41 (1985), S. 1052-1054 
    ISSN: 1420-9071
    Keywords: Cardiac muscle ; phylogenesis ; sarcoplasmic reticulum ; phospholamban ; protein kinase ; Ca2+-transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Phospholamban, a sarcoplasmic reticulum phosphoprotein, is present in the hearts of mammalian, avian, amphibian, and fish species. Phylogenetic changes are indicated by marked differences among species in cardiac phospholamban content and by the absence of Ca2+/calmodulin-dependent phospholamban phosphorylation at an early developmental stage.
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  • 7
    ISSN: 1573-4919
    Keywords: neonatal rat cardiomyocyte culture ; sarcoplasmic reticulum ; phospholamban ; calcium ATPase ; calcium transport ; thyroid hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract This study investigates sarcoplasmic reticulum (SR) calcium-(Ca2+) transport ATPase (SERCA2a) and phospholamban (PLB) in cultured spontaneously contracting neonatal rat cardiomyocytes (CM) to ascertain the function of both SR proteins under various culture conditions. The two major SR proteins were readily detectable in cultured CM by immunofluorescent microscopy using specific anti-SERCA2 and anti-PLB antibodies. Double labeling technique revealed that PLB-positive CM also labeled with anti-SERCA2. Coexpression of SERCA2 and PLB in CM was supported by measurement of cell homogenate oxalate-supported Ca2+ uptake which was completely inhibited by thapsigargin and stimulated by protein kinase A-catalyzed phosphorylation. Under serum-free conditions, incubation of CM with the SERCA2a expression modulator 3,3′,5-triiodo-L-thyronine (100 nM, 72 h) resulted in elevated Ca2+ uptake of +33%. Specific Ca2+ uptake activity was not altered if insulin was omitted from the serum-free culture medium but total SR Ca2+ transport activity was reduced under this culture condition. The results indicate that primary culture of spontaneously contracting neonatal rat CM can be employed as a useful model system for investigating both short- and long-term mechanisms determining the Ca2+ re-uptake function of the SR under defined culture conditions.
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  • 8
    ISSN: 1573-4919
    Keywords: heart ; postnatal development ; sarcoplasmic reticulum ; phospholamban ; calcium transport ; spontaneously hypertensive rats ; growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract This comparative study investigates the relationship between sarcoplasmic reticulum (SR) calcium(Ca2+)-ATPase transport activity and phospholamban (PLB) phosphorylation in whole cardiac homogenates of spo`ntaneously hypertensive rats (SHR) and their parent, normotensive Wistar Kyoto (WKY) strain during early postnatal development at days 1, 3, 6, 12 and at day 40 to ascertain any difference in SR Ca2+ handling before the onset of hypertension. At day 1, the rate of homogenate oxalate-supported Ca2+ uptake was significantly higher in SHR than in WKY (0.25 ± 0.02 vs 0.12 ± 0.01 nmoles Ca2+/mg wet ventricular weight/min, respectively; p 〈 0.001). This interstrain difference disappeared with further developmental increase in SR Ca2+ transport. Western Blot analysis and a semiquantitative ELISA did not reveal any difference in the amount of immunoreactive PLB (per mg of total tissue protein) between strains at any of the ages studied. In addition, levels of phosphorylated PLB formed in vitro in the presence of radiolabelled ATP and catalytic (C) subunit of protein kinase A did not differ between SHR and WKY at days 1, 3, 6 and 12. At day 40, C subunit-catalyzed formation of 32P-PLB was reduced by 66% (p 〈 0.001) in SHR when compared to age-matched WKY In the early postnatal period between day 1 and 12 SR Ca2+-transport values were linearly related to the respective 32P-PLB levels of both SHR and WKY rats. The results indicate that cardiac SR of SHR can sequester Ca2+ at a much higher rate immediately after birth compared to WKY rats. The disappearance of this interstrain difference with further development suggests that some endogenous neuroendocrine or nutritional factor(s) from the hypertensive mother may exert an influence upon the developing heart in utero resulting in a transiently advanced maturation of the SR Ca2+ transport function in SHR pups at the time of birth.
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  • 9
    ISSN: 1573-4919
    Keywords: atria ; thyroid hormones ; β-adrenergic effect ; sarcoplasmic reticulum ; phospholamban
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract This paper discusses the mechanisms of two basic effects of thyroid hormones on atrial responses to β-adrenergic agonists, i.e. increased inotropic sensitivity and decreased maximal contractile responsiveness. The increased sensitivity of atria to β-adrenergic agonists under thyroid hormones appears to be related to increases in β-adrenoceptor density and Gs/Gi protein ratio, leading to activation of Gs-mediated pathway, but suppression of Gi-mediated pathway of adenylate cyclase regulation. Therefore, the i/c concentrations of cAMP and corresponding inotropic responses achieve their maximums at lower doses of β-adrenergic agonist. Thyroid hormones also decrease the expression of phospholamban, but increase the expression of sarcoplasmic reticulum Ca+2-pump. As a result, the basal activity of sarcoplasmic reticulum Ca+2-pump increases, but its β-adrenergic activation through phosphorylation of phospholamban decreases. It is suggested that these changes are causal for decreased maximal inotropic and lusitropic responses of atria to β-adrenergic agonists.
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