Converting enzyme inhibition and vascular prostacyclin synthesis: effect of kinin receptor antagonism.

The effects of angiotensin I-converting enzyme (ACE) inhibitors and bradykinin (BK) on prostacyclin (PGI2) production in isolated arterial tissue were investigated. Rings of rat abdominal aorta were incubated in Krebs-Ringer bicarbonate buffer and PGI2 generation was assessed by the determination of its stable hydrolysis product; 6-keto-PGF1 alpha. The addition of both ACE inhibitors, captopril and lisinopril, and bradykinin resulted in dose-dependent stimulation of PGI2 biosynthesis when the individual substance was added into the incubation buffer at final concentrations between 10(-8) and 10(-5) M. The bradykinin-induced stimulation of PGI2 synthesis was dose dependently inhibited by the BK receptor antagonist, D-Arg[Hyp3, Thi5,8, D-Phe7]BK. The captopril- and lisinopril-induced stimulation of vascular 6-keto-PGF1 alpha production was also significantly decreased when the BK antagonist was added to the incubation medium together with the ACE inhibitors. Our results show that both captopril and lisinopril stimulate PGI2 synthesis in arterial tissue and that this effect may be secondary to changes in the activity of the kinin system.

Cadmium and lead in the smoke of a filter cigarette.

Cadmium and lead were determined in the parts of a filter cigarette after fractional smoking. The partitioning of these elements into the main smoke stream, consisting of particulates and gases, also into the side stream, the ash and the butt was determined. Approximately 70% of the lead mobilized by the smoking process was found in the ash; about 50% of the cadmium was transferred into the side stream. The overall trend shows an increase in the amount of the metals in the main stream as the number of puffs is increased. A model for the behavior of the main stream components within the cigarette was developed and showed a high analogy with the Lambert-Beer law describing the absorption of light.

[Implementing secondary poliomyelitis vaccination]. / Durchführung der Poliomyelitis-Wiederimpfung.

Revaccination is necessary also in poliomyelitis immunisation. Recommendations concerning type and frequency of vaccination vary. According to the results of an investigation in vaccinating patients 10-20 years after the last oral vaccination life vaccine can be administered for revaccination. After more than 20 years patients are seronegative. Therefore, a new basal immunisation is necessary after prevaccination with inactivated vaccine.

Converting enzyme inhibitor ramipril stimulates prostacyclin synthesis by isolated rat aorta: evidence for a kinin-dependent mechanism.

The present study was performed to investigate the effect of the angiotensin I-converting enzyme inhibitor ramipril on vascular synthesis of prostacyclin (PGI2). Administration of ramipril (Hoe 498) to rats significantly stimulated prostacyclin (PGI2) synthesis, quantified by radioimmunoassay of its stable hydrolysis product 6-keto-PGF1 alpha, by portions of the animals' isolated aorta. This effect was maximal at a dose range of 10(-7) mol/kg ramipril. The addition of the active ramipril metabolite ramipril diacid directly into the incubation buffer at final concentrations of 10(-9), 10(-6), and 10(-4) M resulted in a dose-dependent stimulation of 6-keto-PGF1 alpha released by isolated aortic tissue. Pretreatment of rats with aprotinin (40,000 U s.c. 60 min before the incubations) attenuated the ramipril-induced effect on aortic 6-keto-PGF1 alpha synthesis. Our results show that the angiotensin I-converting enzyme inhibitor ramipril stimulates PGI2 synthesis in vascular tissue and that this effect may be secondary to changes in the activity of the kinin system.

[Treatment of experimental immune complex nephritis with indomethacin]. / Therapie der experimentellen Immunkomplexnephritis mit Indomethazin.

Functional, histological and immune-histological examination were performed in altogether 64 Wistar-rats, in order to control the effect of a therapy with 2 mg/kg per body weight indomethazine lasting 2 months at the model of an experimental immune complex nephritis. In 44 rats after presensibilisation an immune complex nephritis was performed by intraperitoneal injections with human serum albumin which were repeated three times a week. 24 glomerulonephritis animals and other 20 animals without glomerulonephritis were daily administered indomethazin through a tube probe, the remaining 20 animals with glomerulonephritis served as untreated control groups. The excretion function of the kidney was tested before the beginning of the experiment, 2 weeks after the beginning of the therapy and the regular serum injections, respectively, and before the end of the experiment by determination of the biological half-life period of 131J-hippuran. In every case one day before this the proteinuria during 24 hours was determined. At the end of the experiment the kidneys were examined histologically and immune-histologically. The results showed that indomethazin does not lead to a clear influence on the proteinuria in the immune complex nephritis of the rat. The excretion of 131J-hippuran was significantly restricted, whereas the histological and immune-histological preparations in the animals with foreign serum injections showed clear changes of the glomeruli in the sense of an early stage of the immune complex nephritis, however, they did not show any essential influence by indomethazin. That is, indomethazin had altogether no favourable effect on the immune complex nephritis of the rat.

Sodium balance as a determinant of prostacyclin production by isolated rat aorta.

The present study investigates whether the synthesis of prostacyclin (PGI2) in isolated rat aorta is dependent on the state of sodium balance of the animals. Three groups of ten rats each were included into the study. Two of them were fed a diet low in NaCl for 10 days with group I receiving 0.9% saline and group II distilled water as drinking fluid. Group III received a regular rat chow containing approximately 0.8 mmol day-1 of sodium, also for 10 days. At the end of the dietary protocol, systolic arterial blood pressure was significantly higher in group I (109.9 +/- 2.4 mmHg) as compared to group II (101.0 +/- 2.4 mm Hg; P less than 0.05) and group III animals (102.2 +/- 1.6 mm Hg; P less than 0.05). Generation of PGI2-like activity was determined in portions of the animals' isolated aorta using a platelet aggregation bioassay following incubation in 0.05 M Tris buffer (pH 9.3) for 12, 15, and 30 min, respectively. During these incubation times, generation of PGI2-like activity averaged 48.6 +/- 3.5, 57.8 +/- 4.3 and 68.3 +/- 3.2 pmol mg-1 in group III animals, which had received the regular rat chow, with similar values in the low salt group II (50.2 +/- 2.5, 57.7 +/- 2.7 and 72.9 +/- 3.7 pmol mg-1). Aortic generation of PGI2-like material was significantly suppressed in the high salt group I (37.5 +/- 2.8, 46.2 +/- 3.2 and 61.3 +/- 4.0 pmol mg-1; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Bacteriologic, histologic and functional studies of the kidney in 5 days' therapy of experimental E. coli pyelonephritis with gentamycin. Comparison with 9 days' therapy]. / Bakteriologische, histologische und Funktionsuntersuchungen der Niere bei 5tägiger Therapie der experimentellen E.-coli-Pyelonephritis mit Gentamycin. Vergleich mit 9tägiger Therapie.

Short-term antibiotic treatment is recommended in infections of the lower urinary tract but its effectiveness is questioned in the upper urinary tract infections. We compared a 5 and a 9 day treatment of experimental E. coli 022 pyelonephritis after unilateral nephrectomy in 127 mal Wistar rats. We used 9 mg gentamycin per kg b.w. twice daily. I131 hippurat excretion was not decreased during the 5 day treatment but was only temporarily diminished during the 9 day treatment. Histologically the severe acute pyelonephritis was decreased after the 9 day treatment but not after 5 days of treatment. Bacteriologically almost all the kidneys were sterile after the 9 day treatment but the majority of the kidneys showed the injected strain of E. coli after the 5 day treatment. The results indicated that the shortened treatment was much less effective in our acute experimental pyelonephritis.

[Kidney function and bacteriological and histological research in the therapy of experimental E. coli pyelonephritis using trimethoprim-sulfamethoxazole (TMP-SMO)]. / Nierenfunktion, bakteriologische und histologische Untersuchungen bei Therapie der experimentellen E.-coli-Pyelonephritis mit Trimethoprim-Sulfamethoxazol (TMP-SMO).

40 uninephrectomized male Wistar rats with an experimental E.-coli-022-pyelonephritis (PN) were treated twice daily for 9 days with 30 mg trimethoprim and 150 mg sulfamethoxazole (TMP-SMO) i.p. Bacteriologically most of the kidneys became sterile. Histologically a significant reduction of the frequency of severe PN was found in the treated group. The biologic half-life of 131I-hippuran indicated a decrease of excretory function which was reversible. Urine osmolality and osmotic clearance were increased after oral water loading in 10 untreated control animals with PN but not in the treated group. The 9 day treatment had a favourable effect bacteriologically, histologically and also on renal function.

[Kidney function in the course of compensatory hypertrophy following unilateral nephrectomy in the Wistar rat]. / Nierenfunktion im Verlauf der kompensatorischen Hypertrophie nach einseitiger Nephrektomie von Wistarratten.

Unilateral nephrectomy was performed in 109 male Wistar rats, 35 animals served as controls. Determinations of glomerular filtration rate (GFR) using slope clearance of 99mTc-DTPA and of tubular function using an orally water-loading test were made. The tests were performed 2 and 5 days as well as 2, 4, 5 and 6 weeks after nephrectomy. In all examinations the GFR was more than 50% of the level of two-kidney control animals. Fractional maximum diuresis was increased in the first 2 examinations after nephrectomy from 8.9 +/- 2.1 to 15.4 +/- 4.2% of the GFR and fractional clearance of osmotically free water from 6.8 +/- 1.9 to 10.9 +/- 3.5%. In the fourth and sixth week the proximal tubular reabsorption was increased and the glomerulo-tubular balance had been recovered. However, the minimal urine osmolarity was increased to 107.8 +/- 17.7 mmol/l and the osmotic load of the nephrons remained elevated. Possible clinical implications of the results are discussed.

Purified verotoxins of Escherichia coli O157:H7 decrease prostacyclin synthesis by endothelial cells.

Two immunologically distinct verotoxins purified from Escherichia coli C600, lysogenized with distinct temperate phages from E. coli strain 933 of serotype O157:H7, were compared by SDS-PAGE and different biological assays. The two toxins termed verotoxin 1 (VT1) and verotoxin 2 (VT2) differing in molecular weight exhibited similar biological activities. Both preparations were toxic for HeLa cells and lethal for mice. Epidemiological evidence of verotoxinogenesis in some cases of hemolytic-uremic syndrome (HUS) and the recent observations of inadequate prostacyclin production by endothelial cells associated with HUS prompted us to study the effect of purified verotoxins on prostacyclin synthesis in rat aortic tissue. Our results demonstrate a significant reduction of prostacyclin by both toxins at picomolar levels. The suppression of prostacyclin release by a lower concentration of VT2 as compared with VT1 reflects the relative potencies of these toxins in HeLa cell toxicity and mouse lethality. The results suggest an effect of verotoxins on endothelial cells and support the concept of these toxins as virulence factors in E. coli.

[Kidney function in spontaneously hypertensive rats under minoxidil treatment]. / Nierenfunktion bei spontan hypertonen Ratten unter Minoxidilbehandlung.

In 25 spontaneously hypertensive rats the blood pressure was lowered from 192 +/- 11.6 to 130 +/- 11.7 mm Hg and in 26 normotensive Wistar rats from 129 +/- 9.1 to 107 +/- 6.7 mm Hg by applying 1 mg/kg body weight minoxidil twice a day orally. 19 spontaneously hypertensive and 21 normotensive rats served as untreated control groups. During the treatment the glomerular filtration rate, determined by the slope clearance of Tc-99m-DTPA, remained unchanged. Under maximal water diuresis the excretion fraction of sodium was diminished compared with the control data. The Na+ and water reabsorption was increased in the proximal tubules (not an aldosterone effect) only in the treated spontaneously hypertensive rats. The potassium clearance was increased in this group, but decreased in the treated normotensive group. The different reactions of the renal tubular function to the treatment with minoxidil in spontaneously hypertensive compared with normotensive rats were discussed in connection with changes of membrane transport in essential hypertension.