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  • 1
    ISSN: 1432-1440
    Keywords: Na-K-ATPase ; Ouabain ; Natriuretic hormone ; Intracellular electrolytes ; Peripheral vascular resistance ; Cardiac function ; Hypertension ; Calcium entry blockade ; Human studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An endogenous humoral factor which inhibits the sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) enzyme in vitro has been incriminated recently of playing a pathogenetic role in experimental and human hypertension. The present study was therefore performed in six healthy volunteers to investigate the hemodynamic consequences of an inhibition of this enzyme by ouabain, a potent and specific inhibitor of Na-K-ATPase. In addition, the role of intracellular calcium as a potential mediator was studied indirectly by the administration of nifedipine, a potent calcium entry blocker with predominant vasodilator properties. Intravenous administration of 8.5 µg ouabain/kg body weight inhibited red blood cell (RBC) — Na-K-ATPase by 49% which was accompanied by a significant increase in RBC — ATP and a decrease in intracellular potassium concentrations. This enzyme inhibition resulted in a 24% increase in peripheral vascular resistance. The parallel decrease in cardiac output and heart rate, however, prevented a rise in arterial pressure. This increase in vascular resistance was completely abolished by pretreatment with nifedipine (10 mg orally). In the absence of an effect of nifedipine on Na-K-ATPase, its attenuation of the vasoconstrictor effect of ouabain suggests that the effects of ouabain on the vascular smooth muscle cell are mediated by intracellular calcium. These results demonstrate that inhibition of the Na-K-ATPase enzyme in vivo causes a marked peripheral vaso-constriction. They are also compatible with the concept that an endogenous inhibitor of Na-K-ATPase — in the presence of decreased baroreceptor reflex sensitivity due to blood volume expansion — may play a role in the pathogenesis of human arterial hypertension.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 57 (1979), S. 863-873 
    ISSN: 1432-1440
    Keywords: Renovascular hypertension ; Renal venous renin activity ; Effect of surgery ; Renovaskuläre Hypertonie ; Nierenvenenreninaktivität ; Operationserfolg
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der vorliegenden Untersuchung wurde das postoperative Blutdruckverhalten bei 35 Patienten mit renovaskulärer Hypertonie untersucht: 17 Patienten mit fibromuskulärer Dysplasie (FMD) und 18 mit arteriosklerotischen Gefäßwandveränderungen (ASS). Patienten mit FMD waren im Mittel jünger (31,8 Jahre), zeigten eine kürzere Hypertonieanamnese (1,8 Jahre) und waren prävalent weiblich (82%), während Patienten mit ASS deutlich älter waren (48,2 Jahre), eine längere Hypertoniedauer (2,6 Jahre) zeigten und bevorzugt männlich (78%) waren. In beiden Gruppen zeigte das intravenöse Pyelogramm einen vergleichbar hohen Anteil positiver Befunde (FMD=64%, ASS=61%). Postoperativ waren in der Gruppe mit FMD 47% (n=8) geheilt, 47% (n=8) gebessert und nur 6% (n=1) der Patienten geringgradig gebessert. Die vergleichbaren Werte für die Gruppe mit ASS betrugen 28, 55 und 17%. Für das Gesamtkollektiv war folglich ein guter Operationserfolg (geheilt und gebessert) in 88,5% der Fälle zu beobachten. Patienten mit ASS und postoperativ nur geringgradiger Besserung (n=3) zeigten eine auffallend lange Hypertonieanamnese (7,0±1,4 Jahre). Bei allen Patienten wurde präoperativ die seitengetrennte Bestimmung der Renin-Aktivität (PRA) im Nierenvenenblut durchgeführt und aus den Werten die PRA-Quotienten (PRA betroffene/nicht betroffene Seite) errechnet. Bei 27 Patienten wurde die Bestimmung 15 und 30 min nach intravenöser Stimulation mit 40 mg Furosemid wiederholt. PRA-Quotienten von ≧1,5 wurden als signifikant bezeichnet. Bei 31 Patienten mit einseitiger renovaskulärer Hypertonie wurde die Höhe des PRA-Quotienten zum postoperativen Blutdruckverhalten korreliert. Dabei zeigte sich zwischen der Gruppe der postoperativ Geheilten und der der postoperativ Gebesserten kein signifikanter Unterschied im mittleren PRA-Quotienten. Ferner ließen sich für das Gesamtkollektiv der 31 Patienten mit einseitiger renovaskulärer Hypertonie unter Ausgangs- und Stimulationsbedingungen keine signifikanten Korrelationen zwischen Höhe der PRA-Quotienten und postoperativem Blutdruckabfall ermitteln. Unsere Ergebnisse unterstützen nicht die weit verbreitete Ansicht, daß sich die seitengetrennte Bestimmung der PRA im Nierenvenenblut als Parameter für den zu erwartenden Operationserfolg bei Patienten mit einseitiger renovaskulärer Hypertonie eignet. Die Methode kann deshalb nach unserer Ansicht nicht mehr als obligater Bestandteile der präoperativen Diagnostik der renovaskulären Hypertonie empfohlen werden.
    Notes: Summary In the present study the effect of surgery on blood pressure was investigated in 35 patients with renovascular hypertension: 17 patients with fibromuscular hyperplasia (FMD) and 18 with atherosclerosis (ASS) of the renal artery. Patients with FMD were younger (31,8 years), showed a shorter duration of hypertension (1.8 years) and were prevalently female (82%), whereas patients with ASS were markedly older (48.2 years), showed a longer duration of hypertension (2.6 years) and were most often male (78%). In both groups of patients the intravenous urogram was positive in a comparable high percentage (FMD=64%, ASS=61%). Following surgical intervention 47% (n=8) of the 17 patients with FMD were cured, 47% (n=8) were improved and only 6% (n=1) showed insufficient reduction of blood pressure values. In ASS the respective values were 28, 55 and 17%. Consequently a good effect of surgery (cured and improved) was observed in 88.5% of all patients. Patients with ASS who failed to respond to surgery (n=3) showed a remarkable long duration of hypertension (7.0±1.4 years). Plasma renin activity (PRA) was determined preoperatively in both renal veins in all 35 patients. From these values the PRA-ratio (PRA affected/unaffected side) was calculated. In 27 patients PRA determinations were repeated following (15 and 30 min) intravenous injection of 40 mg furosemide. PRA-ratios of ≧1.5 were considered to be significant. In 31 patients with unilateral renovascular hypertension PRA-ratios were correlated to the postoperative blood pressure reduction. No significant differences in mean PRA-ratios were observed between cured and improved patients. Furthermore, for the total group of 31 patients no significant correlations were obtained between PRA-ratios and postoperative blood pressure reduction. Our results do not support the widespread opinion that PRA determinations in both renal veins are useful to predict the effect of surgery in patients with unilateral renovascular disease. Therefore, from our experience this method should not be recommended as obligatory in the diagnostic work-up of renovascular hypertension.
    Type of Medium: Electronic Resource
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