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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 36 (1980), S. 865-866 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Rat urine, even at a 1∶10 final dilution in Tyrode's solution, stimulates contraction of the ureteral musculature in vitro. This effect can be ascribed to the presence of kallikrein or a kallikrein-like enzyme in urine. Isometric contractions of ureters were prevented by previous addition of aprotinin to the organ bath. Urine also lost its activity after inactivation of enzymes by heat or acid treatment.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 67 (1989), S. 1069-1076 
    ISSN: 1432-1440
    Keywords: Atrial natriuretic peptide ; Essential hypertension ; Renal failure ; Primary hyperaldosteronism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Atrial natriuretic peptide is a recently discovered cardiac hormone with natriuretic, vasodilatory and hypotensive activities. The role of this hormone in the pathophysiology of hypertension is of particular interest. In contrast to an earlier concept, a deficiency of the atrial peptide could not be found in animal models of hypertension or in patients. ANP plasma levels were elevated in SHR with accelerated hypertension, in salt-sensitive Dahl rats, in rats with DOCA-salt-hypertension and in animals with renovascular hypertension. Elevated ANP levels under these conditions can be explained by an expansion of the intravascular volume or by an elevated atrial wall stretch induced by the hypertension itself. In patients with primary hypertension, plasma levels of the peptide are raised in some patients and are normal in others. Plasma ANP levels correlate with age, blood pressure and signs of left ventricular hypertrophy. A negative correlation is described between ANP and renin. Measurement of plasma ANP levels does not allow a differentiation between primary and secondary forms of hypertension. Elevated ANP levels are also found in primary hyperaldosteronism and in renal failure. Stimulation of ANP secretion by physical exercise and dietary salt loading is maintained in hypertension. Infusion of 1-28-hANP leads to a reduction in systemic arterial pressure in normotensives and hypertensives. The natriuresis induced by exogenous ANP is more pronounced in hypertensives. Stimulation of endogenous ANP secretion does not prevent the rise in blood pressure possibly due to a reduction in ANP receptors in target tissues.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 67 (1989), S. 1085-1095 
    ISSN: 1432-1440
    Keywords: Bradykinin ; Blood pressure ; Prostaglandins ; Kallikrein-kinin system ; Pulmonary circulation ; Hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In our studies we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intraarterially (40–6050 pM/kg) respectively was infused intraarterially (40–6050 pM/kg/min). The investigations were performed in 21 normotensives and 15 hypertensives. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol Na/d), salt loading (300 mmol Na/d), captopril (50 mg), ramipril (5 mg), lisinopril (20 mg), ketotifen (2×1 mg), indomethacin (2×50 mg), and propranolol (80 mg). The results show that bradykinin lowers blood pressure dose related by marked reduction in peripheral vascular resistance. The blood pressure reduction was strongly correlated with the increase in kinin concentration. This effect of bradykinin appears to be independent of changes in sodium metabolism, of betaadrenoceptors, of histamin-1 receptors, and of prostaglandins. ACE-inhibitors potentiate the blood pressure lowering effect of bradykinin about 20- to 50-fold. In case of an intraarterial injection of bradykin in only 2–5% of the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From this experiments a pulmonary clearance rate of bradykinin over 95% can be calculated. In the pulmonary arteries bradykinin has no effect on the vascular resistance. In patients suffering from primary or renovascular hypertension the blood pressure response to bradykinin was enhanced. The bradykinin potentiating effect of the ACE-inhibitors was not altered in the hypertensives. In patients suffering from borderline hypertension or primary hyperaldosteronism bradykinin developed the same blood pressure lowering effect as in the normotensives.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: Furosemide ; Hydrochlorothiazide ; Diuresis ; Kallikrein ; Kinins ; ACE-inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In healthy volunteers the acute effect of furosemide (40 mg i.v.) and hydrochlorothiazide (100 mg p.o.) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated. Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly probably due to a diminished (about 50%) proximal-tubular secretion of furosemide. Captopril did not alter significantly the furosemide induced changes in urinary kallikrein and kinin excretion. After captopril there was a clear dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion. Other ACE-inhibitors like ramipril (5 mg) or enalapril (20 mg) did not influence the stimulatory effects of furosemide on diuresis or kallikrein-kinin excretion. Ramipril at a dose of 10 mg, however, enhanced the initial diuretic effect of furosemide by increased furosemide secretion and increased relative sodium excretion. Hydrochlorothiazide induced a prolonged diuresis which was not changed by either captopril or ramipril. Urinary kallikrein excretion was not stimulated by hydrochlorothiazide. Our results show an important drug interference between captopril and furosemide, which is independent of ACE-inhibition and probably only due to an interference in proximal-tubular secretion of both drugs. Between captopril and hydrochlorothiazide no such interaction could be observed.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Keywords: Human atrial natriuretic peptide ; Sodium ; Primary hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma levels of α-human atrial natriuretic peptide (hANP) were measured in 17 patients with primary hypertension (11 females, 6 males, aged 22–61; blood pressure systolic 154±7 mmHg, diastolic 92±4 mmHg) and in 9 normotensive controls (4 males, 5 females, aged 20–71; blood pressure systolic 117±4 mmHg, diastolic 76±2 mmHg) during unrestricted sodium diet, at the 4th day of a low sodium intake (40–60 mEq/day) and at the 6th day of sodium loading (280–320 mEq/day) both after an overnight rest and after 4 h of upright posture. In the controls, plasma levels of hANP at 8:00 a.m. were lowered from 73±11 to 49±7 pg/ml during low sodium diet and increased to 128±37 pg/ml after high salt intake. Plasma ANP levels were significantly lower after 4 h of upright posture during unrestricted, low and high sodium intake. In the hypertensive group, plasma ANP levels were elevated during unrestricted diet (203±43 pg/ml), during the low sodium period (139±31 pg/ml), and after high sodium intake (267±63 pg/ml) compared to the controls. All levels were lowered by upright posture. The absolute decrease was more pronounced compared to the normotensives, the relative decline was similar in both groups. In the hypertensives, plasma ANP levels significantly correlate with systolic and diastolic blood pressure (r=0.468,r=0.448,P〈0.05) and with urinary aldosterone during unrestricted diet (r=0.536,P〈0.05). There was an inverse correlation between plasma ANP levels and plasma renin concentration during low and high sodium intake (r=−0.469,r=−0.496,P〈0.05). These studies demonstrate raised circulating plasma ANP levels in patients with essential hypertension. The modulation of ANP by different sodium intake and by upright posture is maintained similar to the changes in plasma ANP in normotensive controls. Raised ANP levels in the hypertensives are correlated with low renin secretion and high aldosterone excretion. High ANP levels, therefore, might indicate sodium retention in essential hypertension.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 62 (1984), S. 1097-1101 
    ISSN: 1432-1440
    Keywords: Essential hypertension ; Angiotensin II ; Aldosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Regulation of aldosterone secretion by sodium chloride is impaired in a group of essential hypertensives: high-salt diet fails to suppress aldosterone in these patients despite low renin values. The mechanism of this impaired regulation of aldosterone has not been clarified so far. We tested the sensitivity of aldosterone secretion and blood pressure to A II in 20 normotensive controls (aged 20–60, MAP 92±3 mm Hg), in ten normotensives with one or two parents with hypertension, and in 21 patients with essential hypertension (aged 17–65, MAP 119±4 mm Hg). After a period of 6 days on high-salt intake (300–320 mEq Na+/day), A II (0.1, 0.5, 1.0 and 2.0 ng/kg/min) was infused, each concentration for 30 min. According to aldosterone excretion during sodium loading, patients were divided into group A with complete suppression (n=12, aldosterone excretion 3.6±0.4 µg/day) and in group B with insufficient suppression (n=9, aldosterone excretion 15.5±2.3 µg/day). Despite similarly low plasma renins, rise of serum aldosterone levels during A II infusion was significantly higher in group B patients than in group A patients and normotensive controls. Rise in mean arterial blood pressure, however, brought about by graded A II infusion was similar in both groups of hypertensives and in normotensive controls. The results demonstrate an increased adrenal sensitivity to A II in a subgroup of essential hypertensives only. A similar adrenal hypersensitivity to A II found by others in patients with hyperaldosteronism due to adrenal hyperplasia supports the hypothesis that the same mechanism underlies both disorders.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 15 (1984), S. 111-118 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In male spontaneously hypertensive rats (SHRSP) of the stroke prone strain (Okamoto) and in normotensive Wistar-Kyoto rats (WKY) urinary kallikrein excretion was investigated at different age and at drug-induced diuresis. In rats of both strains from 7th till 19th week of age urinary kallikrein excretion increased with age. In SHRSP of 7th till 11th week of age kallikrein excretion was higher than in WKY rats, while it was lower in the 48-week-old SHRSP. No correlation was found between urinary kallikrein excretion and systolic blood pressure. In SHRSP and WKY rats a similar daily rhythm of kallikrein excretion in urine was found being high in the early morning and low in the afternoon. Kallikrein excretion correlated significantly with urine volume. The loop diuretic bumetanide (4 and 40 mg/kg) induced diuresis and natriuresis in both strains, however more marked in the WKY rats than in the SHRSP. Urinary kallikrein excretion, however, showed in both strains the same biphasic course with a short lasting increase and a secondary decrease. Thus, in the average urinary kallikrein excretion was not effected by the drug. Prolonged treatment with furosemide over 5 days (125 mg/kg) resulted in an increase in kallikrein excretion in urine, more pronounced in the WKY rats than in the SHRSP. The observed results suggest that renal kallikrein-kinin system is not involved in the development of spontaneous hypertension as a pathogenetic factor, but rather is influenced by other factors like hormone interactions, i.e. mineralocorticoids and catecholamines, as well as renal function and acute changes in urine flow.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 38 (1982), S. 941-943 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Adrenalectomy reduces, and sodium depletion increases, both the daily urinary excretion of kallikrein and the kallikrein activity in the renal cortex. These 2 variables were found to correlate significantly in normal, sodium depleted and adrenalectomized rats, thus supporting the view that kallikrein excretion reflects the activity of the enzyme in the kidney.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 313 (1980), S. 155-157 
    ISSN: 1432-1912
    Keywords: Spontaneosly hypertensive rats ; Urinary kallikrein ; Sympathetic activity ; 6-Hydroxydopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Urinary kallikrein excretion was studied in young, stroke-prone, spontaneously hypertensive rats (spSHR). Seven-week-old spSHR were found to excrete more kallikrein into the urine than normotensive Wistar Kyoto control rats (WKR). “Chemical sympathectomy”, induced by 6-hydroxydopamine (6-OHDA) immediately after birth, resulted in normotensive blood-pressure levels and in a reduction of kallikrein in spSHR. In normotensive WKR, blood pressure and urinary kallikrein excretion were only slightly diminished by 6-OHDA. The results suggest a relationship between sympathetic activity and kallikrein excretion, being especially pronounced in spSHR, which have an elevated sympathetic activity.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1440
    Keywords: Aldosteron-Exkretion bei essentieller Hypertonie ; “Low-renin”-Hypertonie ; Spironolacton-Therapie ; Salzbelastung ; Aldosterone excretion in essential hypertension ; Low-renin essential hypertension ; Spironolactone response in essential hypertension ; Sodium loading in essential hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In patients with grade I and II essential hypertension studied during sodium loading (Na+ excretion above 175 meq·d−1) we found a bimodal behaviour of aldosterone excretion and could distinguish two groups of patients: In the major part of essential hypertensives sodium loading led to a suppression of aldosterone excretion below 6 µg·d−1, which is the highest control value during sodium loading, with an average of 2.7±1.4 (SD) µg·d−1. Aldosterone excretion in a second group of patients was not suppressible below 6 µg·d−1 despite forced sodium loading; it resulted in an average value of 10.0±3.0 (SD) µg·d−1. During sodium deprivation or free sodium intake, aldosterone excretion in the first group of patients followed exactly the behaviour of normotensive controls, while in the second group of essential hypertensives the correlation of aldosterone excretion and log. Na excretion or log. Na+/K+ ratio in 24 h urine (r=−0.59) was far below the control value ofr=−0.87. Serum potassium concentration during sodium loading was significantly (p〈0.001) lower (3.81±0.44 meq·l−1) in the essential hypertensives with non-suppressible aldosterone excretion compared to those with suppressible aldosterone excretion (4.26±0.37 meq·l−1). The blood pressure response to treatment with 200 mg spironolactone·d−1 was better (p〈0.05) in patients with non-suppressible aldosterone excretion compared to the essential hypertensives with normal aldosterone regulation. The plasma renin activity of both groups of patients was not significantly different, however, a tendency prevailed towards lower PRA-values in the patient group with non-suppressible aldosterone excretion during sodium loading.
    Notes: Zusammenfassung Bei Patienten mit essentieller Hypertonie Grad I und II fand sich unter Salzbelastungsbedingungen (Natrium-Exkretion über 175 mval·d−1) eine bimodale Verteilung der Aldosteron-Exkretion, aufgrund welcher zwei Patientengruppen unterschieden wurden: Beim größeren Teil der Patienten mit essentieller Hypertonie führte die Salzbelastung zu einer Suppression der Aldosteron-Exkretion unter 6 µ·d−1, dem höchsten Kontrollwert unter Salzbelastung, im Durchschnitt zu 2,7±1,4 (SD) µg·d−1. Trotz ausgeprägter Salzbelastung über 6 Tage war die Aldosteron-Exkretion bei einer zweiten Gruppe nicht unter 6 µg·d−1 supprimierbar mit einer durchschnittlichen Aldosteron-Exkretion von 10,0±3,0 (SD) µg·d−1. Unter Salzentzug, freier Salzzufuhr oder Salzbelastung war die Aldosteron-Exkretion der ersten Gruppe der der Kontrollpersonen vergleichbar, während bei der zweiten Gruppe der essentiellen Hypertoniker die Korrelation zwischen Aldosteron-Exkretion und Log Natrium-Exkretion oder Log Natrium/Kalium-Quotient im 24 h-Urin (r=−0,59) deutlich unter der der Kontrollpersonen (r=−0.87) lag. Die Serum-Kalium-Konzentration unter Salzbelastung der zweiten Hypertonikergruppe mit nicht supprimierbarer Aldosteron-Exkretion war signifikant (p〈0,001) niedriger (3,81±0,44 mval·l−1) als bei den übrigen Hypertonikern mit supprimierbarer Aldosteron-Exkretion (4,26±0,37 mval·l−1). Die Blutdrucksenkung unter 200 mg Spironolacton täglich war bei den Patienten mit nicht supprimierbarer Aldosteron-Exkretion signifikant (p〈0,05) besser als beim Rest der Patienten. Die Plasmareninaktivität beider Gruppen war noch nicht signifikant unterschiedlich, zeigt jedoch eine Tendenz zu niedrigeren Werten in der Gruppe mit nicht supprimierbarer Aldosteron-Exkretion.
    Type of Medium: Electronic Resource
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