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H Vetter

Publications and source records attributed to H Vetter.

At least 19 recordsLinked to original sources
PubMed1992

Angiotensin II induces formation of the early growth response gene-1 protein in rat vascular smooth muscle cells.

The effect of angiotensin II (Ang II) on the early growth response gene-1 (Egr-1) mRNA, on the Egr-1 protein and on the phosphoinositide PI turnover signalling system was investigated in the presence and absence of EXP3174, a potent non-peptide Ang II receptor antagonist. Ang II induced an accumulation of 3.4 kb Egr-1 mRNA and the 80 kDa Egr-1 protein, with a maximum at 30 min and 60 min, respectively. EXP3174 blocked the Ang II-induced increase of inositol phosphates, Egr-1 mRNA and the Egr-1 protein, suggesting the involvement of the PI signalling system by the expression of the Egr-1 gene.

Angiotensin II↗
PubMed1992

[Advantages of 24-hour ambulatory blood pressure monitoring for the assessment of dose-effect relations and dose-equivalency].

Because of the high variability of blood-pressure, clinical studies using casual measurements require rather large numbers of patients for assessment of pharmacologic efficacy. By the use of blood-pressure monitoring over 24 hours this number can be dramatically reduced. Additional benefits are the precise determination of dose-effect relationships and the more accurate estimate of the response-rate. Comparing two retarded galenic forms of Verapamil we show that even dose-equivalence can be studied with this type of blood-pressure recording.

Blood Pressure↗
PubMed1992

Losartan inhibits the angiotensin II-induced stimulation of the phosphoinositide signalling system in vascular smooth muscle cells.

2-n-Butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl-4-yl)methyl]imidazole, potassium salt (Losartan) (previous name, DuP 753 or MK 954) is a nonpeptide angiotensin II receptor antagonist. This study was performed to investigate the ability of Losartan to inhibit the angiotensin II-induced stimulation of the phospoinositide signalling system and the angiotensin II-induced hypertrophy in aortic vascular smooth muscle cells of normotensive Wistar-Kyoto rats. 10(-7) M Losartan abolished the angiotensin II-induced formation of inositol 1,4,5-trisphosphate in vascular smooth muscle cells. 10(-6) M Losartan completely abolished the angiotensin II-induced elevation of the intracellular free Ca2+ concentration ([Ca2+]i). 10(-6) M Losartan lacked effects on the [Arg8]vasopressin-induced elevation of [Ca2+]i. In addition, 10(-6) M completely inhibited the angiotensin II-induced stimulation of Na+/H+ exchange in the vascular smooth muscle cells. 10(-10) to 10(-6) M Losartan inhibited the angiotensin II-induced cell protein synthesis in a concentration-dependent manner, yielding to an effective concentration (ED50) of 6.2 +/- 1.8 x 10(-8) M (n = 4). Losartan did not affect the platelet-derived growth factor-BB-induced increase in cell protein. These results show that Losartan is a highly specific angiotensin II receptor antagonist which inhibits angiotensin II-induced cell growth and thus may have beneficial effects on the development and regression of vascular hypertrophy.

Angiotensin II↗
PubMed1992

[Adrenal cortex carcinoma: diagnosis, therapy and course in 10 cases].

Data from ten cases with carcinoma of the adrenal cortex, diagnosed between 1981 and 1988, have been extensively reevaluated. Six patients suffered from a hormonally active tumor with proven clinical and laboratory signs of hypercortisolism and/or hyperandrogenism. Female patients dominated the cohort (eight of ten). No preference for particular age (35 to 64, mean 52) or lateralisation of the tumor was recognisable. In all cases signs for endocrinopathy and/or tumor disease lead to investigative intervention. Nonspecific symptoms like pain, reduction of weight and fatigue were registered most frequently. In three patients an abdominal tumor was palpable. Investigation of hormone levels and imaging procedures (sonography and CT scan) assured correct diagnosis in all cases. Since prior to operation metastases have been detected in five cases and in eight cases capsular invasion was proven histologically only, one patient was free of tumor after operation but developed hepatic metastases later on. Altogether nine of ten patients developed metastases later on. Seven of the patients died from the perioperative period up to 8.4 +/- 8.15 months. Mean survival of all patients was 20.5 +/- 24.5 months. Histological grading and assessment of anaplasia did not correlate with either survival or tumor stage. None of the patients presented with tumor stage I according to the TNM system by MacFarlane (55). All four patients with advanced disease in stage IV died within the first year after operation. Eight patients were treated with 1 to 6 g of the adrenolytic o,p'DDD (mitotane, Lysodren). In one of these cases, a sonographically documented remission lasting for over eight years was observed. A second patient with anaplastic carcinoma showed a reduction of the size of pulmonary metastases under continuous therapy with o,p'DDD and a cyclic polychemotherapy. After the latter was discontinued, the course was progressive.

Adrenal Cortex Hormones↗
PubMed1992

Effects of a high-cholesterol diet on arterial wall thickness and vascular reactivity in young rabbits.

Cholesterol enrichment of arteries may induce biochemical and structural abnormalities in vascular smooth muscle resulting in increased arterial contractile sensitivity. We studied the effects of a high-cholesterol diet on arterial structural properties and vascular reactivity in young rabbits. In vivo measurements of aortic intimal-plus-medial thickness using high resolution ultrasound imaging were obtained before and after 3 weeks of a high-cholesterol diet in 12 rabbits (group 2) and compared to data from 12 animals a cholesterol-free diet fed (group 1). Six rabbits (group 3) were studied before and after a 3-week, high-cholesterol diet and after a subsequent 13-week, cholesterol-free recovery diet. Blood pressure responsiveness to noradrenaline was evaluated before and at the end of each diet period. In groups 2 and 3, high dietary cholesterol caused an increase in intimal-plus-medial thickness from 0.31 mm and 0.33 mm to 0.88 mm and 0.89 mm, respectively (p less than 0.001). Plasma cholesterol concentration rose from 0.9 +/- 0.26 mmol/l to 36.7 +/- 8.56 mmol/l. There was no change in group 1. In group 3, intimal-plus-medial thickness remained increased (1.01 mm) following the cholesterol-free recovery diet despite normal plasma cholesterol. Blood pressure responsiveness to noradrenaline was markedly increased after the high-cholesterol diet (p less than 0.001) in groups 2 and 3 and after the cholesterol-free recovery diet in group 3 (p less than 0.001), and was directly related to intimal-plus-medial thickness (r = 0.84; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Inhibition of angiotensin II and platelet-derived growth factor-induced vascular smooth muscle cell proliferation by calcium entry blockers.

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 microM 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 microM, while no significant influence was seen with concentrations from 10 nM up to 1 microM. 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.

Angiotensin II↗
PubMed1992

Inhibition of cyclooxygenase attenuates baroreceptor function and increases the pressor response to norepinephrine in man.

The possible influence of prostaglandins on baroreceptor function in man has been investigated. Baroreceptor reflex was activated by intravenous infusion of norepinephrine and the pressor response was measured, both before and after administration of indomethacin. Resting blood pressure remained unchanged after indomethacin while resting heart rate was significantly decreased as compared to placebo and the norepinephrine-induced rise in mean arterial blood pressure was significantly more pronounced. The baroreceptor-mediated decrease in heart rate tended to be smaller. Baroreceptor sensitivity (delta heart rate/delta blood pressure) was significantly reduced by indomethacin to about half of the control value. In addition to attenuation of sensitivity, the findings represent resetting of the baroreceptor setpoint and a more pronounced pressor response to norepinephrine after cyclooxygenase inhibition. Thus, eicosanoids originating via the cyclooxygenase pathway of arachidonate metabolism may modulate the vascular response to adrenergic stimulation and may participate in the regulation of baroreceptor reflex setpoint and sensitivity.

Adult↗
PubMed1992

Platelet cAMP and cGMP in essential hypertension.

Vasodilator substances released in the blood vessel wall, such as the endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2), may participate in the regulation of arterial blood pressure. However, their role in the pathogenesis of human essential hypertension to date remains unclear. For some of these factors affecting vascular smooth muscle cells, blood platelets represent a second target tissue. Thus, EDRF and PGI2 inactivate platelets by stimulation of cyclic guanosine-5'-monophosphate (cGMP) and cyclic adenosine-5'-monophosphate (cAMP) synthesis, respectively. In the present study, platelet cAMP (n = 68) and cGMP (n = 60) were determined in a control group of healthy subjects (C) and in 12 patients with untreated essential hypertension (EH). In the control group, platelet cAMP and cGMP content averaged 13.52 +/- 0.38 and 1.48 +/- 0.06 pmol/10(9) platelets and no dependence of either variable on sex or age could be established. Furthermore, cGMP levels were similar in EH as compared to the control group (1.38 +/- 0.11 pmol/10(9) platelets). However, intracellular concentrations of cAMP were significantly lower in EH as compared to C (11.22 +/- 1.37 pmol/10(9) platelets; P < .01). In addition, we investigated the stimulatory effect on cAMP of the stable PGI2 analog iloprost (10(-9), 5 x 10(-9), 10(-8), 5 x 10(-8) mol/L) in the platelets of 12 control subjects (C12) and EH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The effect of angiotensin II on DNA synthesis varies considerably in vascular smooth muscle cells from different Wistar-Kyoto rats.

OBJECTIVE: It is well established that angiotensin II induces vascular smooth muscle cell (VSMC) growth but conflicting data exist concerning whether angiotensin II induces cell hypertrophy and/or DNA synthesis from Wistar-Kyoto (WKY) rats. DESIGN: In this study we examined the effect of 10(-7) mol/l angiotensin II on cell protein and DNA synthesis in VSMC (passages 5-30) derived from eight different WKY rats. METHODS: The mitogenic and hypertrophic effect of angiotensin II was determined by 3H-thymidine incorporation into cell DNA and by total cellular protein measurements. RESULTS: In cells derived from two cell lines, angiotensin II induced a potent mitogenic effect. In cells derived from two other cell lines it induced a weak mitogenic effect. No significant effects on DNA synthesis were observed in cells derived from the four remaining cell lines. Cells from all cell lines reacted to angiotensin II with a 30-40% increase in cell protein. The observed mitogenic effect of angiotensin II was inhibited by losartan, a non-peptide angiotensin II receptor antagonist, proving that the angiotensin II-induced mitogenic effect is directly triggered via the angiotensin II subtype AT1 receptor. The hypertrophic effect of angiotensin II was also illustrated by morphological studies showing that angiotensin II increases the cell size in all cell lines used. CONCLUSIONS: Our study shows that angiotensin II not only is a hypertrophic agent, but may also be a potent mitogenic agent for VSMC from WKY rats.

Angiotensin II↗
PubMed1992

Action of metoprolol, enalapril, diltiazem, verapamil, and nifedipine on cell growth of vascular smooth muscle cells.

The influence of nifedipine, verapamil, diltiazem, metoprolol, and enalapril on the basal and angiotensin II (Ang II)-induced elevation of [3H]thymidine incorporation into vascular smooth muscle cell (VSMC) DNA was examined. Our results from four independent experiments, each performed in triplicate, are summarized by calculating the half-maximal inhibitory concentration (IC50) of the drugs. Nifedipine, verapamil, and diltiazem had IC50 values of 2.3 +/- 0.7 x 10(-6), 3.5 +/- 0.3 x 10(-6), and 6.6 +/- 2.8 x 10(-6) M, respectively. Metoprolol had an IC50 value of 49 +/- 16 x 10(-6) M, whereas enalapril was completely ineffective. All drugs used had no influence on the basal cell [3H]thymidine incorporation. This in vitro study allows one to conclude that the calcium-entry blockers can inhibit the Ang II-induced cell growth and thus may have beneficial effects on the development and regression of vascular growth, which is associated with the pathogenesis of cardiovascular diseases.

Animals↗
PubMed1992

Pavlovian conditioning of corticotropin-releasing factor-induced increase of blood pressure and corticosterone secretion in the rat.

Corticotropin-releasing factor (CRF) is clearly involved in the central regulation of the pituitary-adrenal axis and, moreover, of autonomic nervous system functions. Enhanced sympathetic activity with subsequent increases in blood pressure and heart rate and attenuation of the baroreceptor reflex results from the intracerebroventricular (i.c.v.) administration of CRF. Additionally, the peptide has a variety of potent effects on behavioural responses in animals similar to those observed after an experimentally evoked stress. It was therefore of obvious interest to examine whether CRF is a possible mediator of the learning processes associated with physiological stress reaction patterns. This report clearly demonstrates a classical conditioning of the endocrine (i.e. corticosterone secretion) and haemodynamic (i.e. blood pressure) sequelae following central CRF application and thus indicates that this mechanism is of physiological significance for learned stress responses.

Animals↗
PubMed1992

[Incidence, prevention and therapy of cytomegalovirus and pneumocystis carinii infection after heart transplantation].

Diseases caused by cytomegalovirus (CMV) and pneumonia due to pneumocytis carinii (PCP) are problematic complications after allogeneic heart transplantation. Recipients of CMV-seropositive donors have a higher morbidity of CMV. By using an anti-CMV-immunoglobulin preparation in routine prophylaxis the incidence of CMV disease after heart transplantation could be reduced significantly. Ganciclovir 10 mg/kg is administered for treatment of CMV disease for at least 14 days. Recent investigations show that a prophylactic administration of ganciclovir after heart transplantation is safe, and it reduces the incidence of CMV-induced illness in CMV-seropositive patients. The incidence of PCP after heart transplantation varies according to the literature between 1 and 13%. The onset of the disease is located mostly between the third and the fifth month after heart transplantation. An effective prophylaxis can be achieved by low dose cotrimoxazole (960 mg at two days per week in adults) within the first six postoperative months. Cases of PCP are treated by cotrimoxazole or pentamidine and are associated with a mortality up to 60%.

Antibodies, Fungal↗
PubMed1992

[Functional aspects of healing in microsurgical tubal anastomosis--experimental studies of the rabbit fallopian tube].

Ovarian function and fertility was studied in 46 female New Zealand White rabbits after isthmic-isthmic reanastomosis of the oviduct. Postoperative ovarian function was slightly suppressed and returned to normal after two month. No significant differences were found between the control side and the side of anastomosis. Fertility was reduced directly after surgery on the side of anastomosis as well as on the control side. On the side of reanastomosis a continuous increase of tubal function occurred up to two month after surgery. At this time tubal function was reduced to 30%, the nidation index was about 0.6. Tubal function of the untreated oviduct was nearly normal (nidation index 0.8) two weeks after surgery.

Animals↗
PubMed1992

Lack of oral kallikrein in lowering systemic blood pressure in primary hypertension.

Primary hypertension is associated with a lack in renal kallikrein activity which might be one of the reasons for the blood pressure elevation. Some smaller and partially uncontrolled studies suggested that an oral substitution of glandular kallikrein lowers blood pressure by a kinin-mediated vasodilation and increased natriuresis. To test this hypothesis we treated in two studies over 100 patients with untreated mild to moderate primary hypertension (WHO I-II) for 5 resp. 12 weeks in a double blind randomized and placebo controlled manner with 1800 U glandular kallikrein orally. Blood pressure measurements were performed according to the two study designs after 3 and 5 resp. 8 and 12 weeks of treatment sphymomanometrically in the day time course. No significant changes in blood pressure by kallikrein treatment could be observed at any time. Neither renal kallikrein excretion, renin and ACE-activity nor blood glucose concentration in diabetics or non-diabetics was changed. Thus, we could undoubtedly demonstrate that oral applied glandular kallikrein has no effect on primary hypertension.

Administration, Oral↗
PubMed1991

Inhibition of endothelin-1 induced myocardial protein synthesis by an antisense oligonucleotide against the early growth response gene-1.

We explored the role of the recently discovered "early growth response gene-1 (Egr-1)" in the induction of myocardial protein synthesis by endothelin-1. Endothelin-1 stimulated protein synthesis (i.e. 3H-phenylalanine incorporation) in isolated adult rat cardiomyocytes more than 2-fold. Addition of a 15mer Egr-1 antisense oligodeoxyribonucleotide complementary to the first 5 codons of the Egr-1 mRNA completely blocked endothelin-induced protein synthesis. A single base mismatch in the oligonucleotide sequence abolished the inhibitory effect. T3-induced stimulation of protein synthesis was unaffected by the antisense oligonucleotide. These results indicate that the Egr-1 gene product is involved (putatively as a third messenger) in the signal transduction cascade initiated by endothelin-1 which eventually culminates in the induction of cardiac protein synthesis.

Animals↗