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G Wambach

Publications and source records attributed to G Wambach.

At least 19 recordsLinked to original sources
PubMed2001

Modulation of noradrenaline-induced microvascular constriction by protein kinase inhibitors.

We have tested the role of various protein kinases in noradrenaline-induced, alpha1A-adrenoceptor-mediated constriction of mesenteric and intrarenal rat microvessels. The protein kinase C inhibitors, H7 and staurosporine, inhibited constriction in both vessel types in concentrations which also inhibit myosin light chain kinase. The more selective protein kinase C inhibitors, bisindolylmaleimide I and Gö 6976, did not inhibit microvessel constriction in concentrations selective for protein kinase C. Moreover, the protein kinase C-activating phorbol ester, phorbol-12-myristate-13-acetate, did not cause constriction. The tyrosine kinase inhibitors, genistein and tyrphostin 23, inhibited constriction in concentrations compatible with tyrosine kinase inhibition. An inhibitor of the extracellular signal-regulated kinase cascade, PD 98059, also caused concentration-dependent inhibition. While chelation of extracellular Ca2+ abolished noradrenaline-induced constrictions, the Ca2+-ATPase inhibitor, thapsigargin, had no effects. We conclude that tyrosine kinases and extracellular signal-regulated kinase (but not protein kinase C) may be involved in noradrenaline-induced rat mesenteric and intrarenal microvessel constriction but this appears to occur independently of an effect on sarcoplasmic Ca2+ storage.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

Evaluation of the efficacy and tolerability of a low-dose combination of isradipine and spirapril in the first-line treatment of mild to moderate essential hypertension.

To investigate the concept of initiating therapy with low doses of a calcium antagonist and an ACE inhibitor, a fixed combination of isradipine 2.5 mg plus the ACE inhibitor spirapril 3 mg was compared with its components, with the full-dose monotherapies (isradipine 5 mg or spirapril 6 mg), and with placebo. After a 2-week wash out phase in pretreated patients and a subsequent 2-week placebo period, 405 patients with a diastolic blood pressure (DBP) between 100 and 114 mmHg were randomly allocated to 12-week once-daily double-blind treatment in one of the six treatment arms. In patients whose blood pressure was not normalized (defined as DBP< or =90 mmHg) after 6 weeks of treatment, the dosage of either medication was doubled or, in the placebo group, was switched to the fixed combination. After week 6, the mean reductions from baseline in sitting systolic/diastolic blood pressure 24 hours after dosing (trough) for the fixed combination or the monotherapies isradipine 5 mg, isradipine 2.5 mg, spirapril 6 mg, spirapril 3 mg, and placebo were 10.4/8.7, 10.0/9.4, 6.5/6.7, 10.0/8.3, 7.0/5.8, and 2.2/4.7 mmHg, respectively. The blood pressure changes obtained with the low-dose fixed combination were essentially identical to those observed with the full-dose monotherapies, thus showing an additive effect of low-dose isradipine and spirapril. In terms of tolerability, the lowest rate of any adverse events was found in the combination group. In this group, typical adverse events of calcium antagonists, such as headache, flushing, ankle edema, or palpitations, were observed only in 5%, 2%, 1%, and 0%, respectively, dry cough, considered typical for ACE inhibitors, was observed in only 1% of the combination group. In conclusion, the low-dose components isradipine 2.5 mg and spirapril 3 mg were shown to have an additive effect when combined, exerting a blood pressure-lowering effect comparable with the full doses and a trend to a better tolerability profile in comparison with the standard doses. Thus, low-dose combination therapy with these drugs appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.

Adult↗
PubMed1997

Vasoconstriction of rat renal interlobar arteries by noradrenaline and neuropeptide Y.

1. We have studied the contractile effects of noradrenaline and neuropeptide Y given alone and in combination on isolated rat renal interlobar arteries. 2. Noradrenaline contracted proximal and distal intrarenal microvessels in a concentration dependent manner, with similar potency (EC50 approximately equal to 550 nM), but maximal effects were greater in the proximal than in the distal vessel segments (approximately equal to 10 and 6 nM, respectively). 3. The noradrenaline-induced contraction was inhibited by low prazosin concentrations (3-10 nM) but not by 1 microM yohimbine indicating involvement of alpha(1)-but not alpha(2)-adrenoceptors. The alpha(1)A-adrenoceptor-selective antagonist, 5-methylurapidil and tamsulosin, had high potency (apparent affinities of approximately equal to 8 nM and 57 pM, respectively) while the alpha(1)D-adrenoceptor-selective antagonist, BMY 7378, had only low potency (apparent affinity approximately equal to 300 nM). The alpha(1)B-adrenoceptor-alkylating agent, chloroethylclonidine (10 microM for 30 min at 37 degrees C), had no inhibitory effects. The Ca2+ entry blocker, nitrendipine (300 nM), reduced the potency and maximal effects of noradrenaline. 4. Neuropeptide Y (1-100 nM) also contracted interlobar arteries in a concentration dependent manner, with greater effects in the proximal than in the distal segments, but maximal effects were only small in either segment (< 2 mN). In addition, neuropeptide Y also potentiated the response to noradrenaline, i.e. lowered its EC50 but this enhancement was also small. 5. We conclude that noradrenaline contracts rat interlobar arteries by an alpha(1)A-adrenoceptor; its co-transmitter, neuropeptide Y, affects the response only marginally in this vascular bed.

Adrenergic alpha-Antagonists↗
PubMed1996

Effects of noradrenaline and neuropeptide Y on rat mesenteric microvessel contraction.

We have studied the contractile effects of the sympathetic transmitter noradrenaline and its cotransmitter neuropeptide Y (NPY) given alone and in combination on isolated rat mesenteric resistance vessels (200-300 microns diameter). Noradrenaline and NPY each concentration-dependently contracted rat mesenteric microvessels (EC50 approximately equal to 800 nM and 10 nM, respectively), but noradrenaline caused considerably greater maximal effects than NPY (14.3 mN vs. 3.5 mN). A low antagonistic potency of yohimbine indicated that the response to noradrenaline did not involve alpha 2-adrenoceptors, and the subtype-selective antagonists 5-methylurapidil, tamsulosin and chloroethylclonidine indicated mediation via an alpha 1A-adrenoceptor. Shallow Schild regressions for prazosin and 5-methylurapidil indicated that an alpha 1-adrenoceptor subtype with relatively low prazosin affinity might additionally be involved. Studies with the NPY analogues PYY, [Leu31, Pro34] NPY and NPY18-36 demonstrated that NPY acted via a Y1 NPY receptor. In addition to its direct vasoconstricting effects NPY also lowered the noradrenaline EC50 but did not appreciably affect maximal noradrenaline responses indicating possible potentiation. The potentiating NPY response occurred with similar agonist potency as the direct contractile NPY effects and also via a Y1 NPY receptor. The Ca2+ entry blocker nitrendipine (300 nM) reduced direct contractile responses to noradrenaline and NPY but did not affect the potentiation response to NPY.

Animals↗
PubMed1995

BNP plasma levels during acute volume expansion and chronic sodium loading in normal men.

Since the isolation of porcine brain natriuretic peptide (pBNP) in 1988, many aspects of this new endocrine and paracrine system have been elucidated. However, the precise role of human BNP (hBNP) in the regulation of sodium balance and blood pressure in men is still unclarified. We investigated the impact of acute volume expansion and high sodium intake on ANP and BNP plasma levels of 21 healthy male subjects. Following acute infusion of 2000 ml 0.9% saline into a peripheral vein over 30 minutes in a lying position, ANP levels in plasma increased from 110 +/- 14 pg/ml to 199 +/- 18 pg/ml (p < 0.001), while BNP levels remained constant (26 +/- 3 pg/ml before, 28 +/- 3 pg/ml after volume expansion). In a second experiment we investigated the change of ANP and BNP plasma levels after five days of controlled sodium intake (Here blood tests were taken from the probands in an upright position). ANP levels averaged 42 +/- 5 pg/ml after low and 73 +/- 14 pg/ml after high sodium intake. Before starting the diet, the ANP fasting blood level was 56 +/- 6 pg/ml. During both diets, plasma BNP was not altered significantly, but we found a slight insignificant increase after high sodium intake. At the end of each diet we tested ANP and BNP secretion by a physical exercise in an upright position. After high salt intake, BNP plasma levels rose from 32 +/- 4 pg/ml at rest to 45 +/- 7 pg/ml (p < 0.025) after 15 minutes of exercise, while ANP rose from 73 +/- 14 pg/ml to 120 +/- 20 pg/ml (p < 0.001). These results suggest a different regulation of ANP and BNP in normal subjects. ANP secretion is modulated by volume loading and by low or high salt intake while BNP responses to physical exercise.

Adult↗
PubMed1993

[Vena cava ultrasonography for the assessment of hydration status in kidney insufficiency].

Vena cava diameter (VCD) was measured by ultrasonography in 10 acutely hypervolemic dialysis patients (6 men, 4 women; mean age 61.3 +/- 15.4 years), results being compared with the level of the central venous pressure (CVP) and, in 39 long-term dialysis patients (18 men, 21 women; mean age 56 +/- 15 years), with the plasma concentration of atrial natriuretic peptide (ANP). In 86 subjects without renal disease (43 men, 43 women; mean age 39.4 +/- 14.6 years) there was a statistically highly significant correlation between the end-expiratory VCD and heart rate (r = -0.63; P < 0.001). These data were used to construct a VCD/heart rate (HR) nomogram. In the ten dialysis patients HR-adjusted VCD correlated significantly at various hydration states (54 measurements) with the CVP (r = 0.72; P < 0.001). The steep slope for the relationship between CVP and VCD showed marked interindividual variations. However, in all patients (except one) with a raised CVP (> 12 cm H2O) the HR-adjusted VCD was above the 95th percentile. In the 39 patients on long-term dialysis (13 with, 25 without predialysis tricuspid regurgitation [TR] there occurred a parallel decrease in VCP and ANP during removal of fluid. In the 25 patients without TR, the fall in ANP concentration and VCD correlated significantly (r = 0.70; P < 0.001). These results indicate that, in patients with renal failure but normal cardiac function, measurement of the VCD by ultrasonography provides an adequate index of hydration.

Adult↗
PubMed1993

The actions of lovastatin on platelet function and platelet eicosanoid receptors in type II hypercholesterolaemia. A double-blind, placebo-controlled, prospective study.

We have studied the effects of 12 weeks of lovastatin (20 mg per day) on platelet function and thromboxane formation in 18 patients with type II hypercholesterolaemia in a double-blind, placebo-controlled, prospective study. Lovastatin significantly reduced total serum and LDL-cholesterol by 20% and 25% respectively. Washed platelets of lovastatin-treated patients had significantly reduced collagen-induced aggregation and thromboxane formation ex vivo. There was no change in ADP-induced platelet aggregation, but a significant increase in prostacyclin (iloprost)-stimulated platelet cyclic AMP concentrations in lovastatin-treated patients. This was associated with a significant increase in the number of prostacyclin receptors in platelet membranes prepared from lovastatin-treated patients. There was also an increase in platelet thromboxane receptors. There were no such changes in the placebo group. These data confirm our original observation of normalization of platelet function in hypercholesterolaemia by HMGCoA reductase inhibitors and suggest changes in platelet membrane composition at the megakaryocyte level as a possible site of action.

Adolescent↗
PubMed1992

[How reliable is oscillometric blood pressure determination at the finger using the Omron device?].

The precision of oscillometric blood-pressure measurements on the finger with the model HEM-812F, manufactured by Omron, was compared to the standard method. The digital measurements from 180 inpatients (115.0 +/- 1.2 mmHg systolic, 68.8 +/- 0.8 mmHg diastolic) were significantly lower than oscillometric measurements from the upper arm using a Bosomat (121.3 +/- 1.4 mmHg systolic, 74.2 +/- 0.9 mmHg diastolic). Correlation coefficients were r = 0.713 for systolic and r = 0.683 for diastolic values, with significant variance of individual values. In direct comparison of the two methods immediately after ergometry the differences were even greater (57 mmHg systolic, 32 mmHg diastolic). Significantly lower digital pressures at the finger were noted in comparison with direct blood-pressure measurements after punction of the femoral artery. Because of significant differences of blood-pressure measurements compared to the Riva-Rocci method, the digital measurement with the HEM-812F device (Omron) can not be generally recommended.

Blood Pressure Determination↗
PubMed1992

[Does the captopril test improve the diagnosis of primary hyperaldosteronism?].

Plasma concentrations of renin and aldosterone were measured before and 60 min after taking 25 mg captopril in 242 patients with arterial hypertension (124 men, 118 women, aged 51.9 +/- 12.7 years; unilateral aldosterone-producing adrenal adenoma in 8, idiopathic hyperaldosteronism in 16 and essential hypertension in 189). Basal plasma aldosterone levels were twice as high in those with adenoma or hyperaldosteronism (216.9 +/- 99.1 pg/ml and 256 +/- 123 pg/ml, respectively) as in those with essential hypertension (117.7 +/- 115 pg/ml). Basal renin levels in adenoma and idiopathic hyperaldosteronism (1 +/- 0.8 microU/ml and 2.6 +/- 1.9 microU/ml, respectively) were decreased compared with those in essential hypertension (13.1 +/- 14.2 microU/ml). The basal aldosterone/renin ratio was higher in adenoma (436 +/- 370 pg/microU) and idiopathic hyperaldosteronism (615 +/- 950 pg/microU) than in essential hypertension (52.9 +/- 151.3 pg/microU). The sensitivity of this ratio in combination with the aldosterone concentration was 100% for recognizing an adrenal adenoma, its specificity 92.7%. The mean plasma aldosterone level after captopril administration did not change in adenoma patients, but fell to 162 +/- 85 pg/ml (P less than 0.001) in those with idiopathic hyperaldosteronism. These data indicate that the captopril test contributes to distinguishing primary from idiopathic hyperaldosteronism.

Adenoma↗
PubMed1991

Severe hypoaldosteronism due to corticosterone methyl oxidase type II deficiency in two boys: metabolic and gas chromatography-mass spectrometry studies.

Infection-triggered, life-threatening salt-loss and hyperkalaemia developed in two male infants with wasting, inappropriately low plasma aldosterone concentrations and elevated plasma renin activity. The presumptive diagnosis of a defective terminal step in aldosterone biosynthesis was made by the presence of large amounts of 11-dehydrotetrahydrocorticosterone and its 18-hydroxylated metabolite (18-OH-THA), free 18-hydroxycorticosterone (18-OH-B) and 18-hydroxytetrahydrocorticosterone in the urine of both patients. The diagnosis of corticosterone methyl oxidase type II (CMO II) deficiency was confirmed by an elevated urinary 18-OH-THA to tetrahydroaldosterone ratio in one boy and by an elevated plasma 18-OH-B to aldosterone ratio in the other boy. Unknown steroids responsible for the salt-loss were not identified. Sodium supplementation but not short-term high dose oral 9 alpha-fluorcortisol (FF) normalized the hyponatraemia in one patient, in whom sodium (Na+)/potassium (K+) co-transport was decreased. Both patients eventually received long-term FF treatment to prevent impairment of longitudinal growth caused by chronic salt-loss. The diagnosis of CMO II deficiency should always be confirmed by elevated precursor-product ratios in urine or plasma, using radioimmunoassays with prior chromatographic separation. Metabolic studies as the short-term response of serum Na+ to high dose FF may not be helpful in differentiating aldosterone biosynthetic defects from end-organ resistance to mineralocorticoids.

Cortisone↗
PubMed1991

[Determination of plasma atrial natriuretic peptide in follow-up of hypervolemic hemodilution in patients with retinal circulatory disorders].

We measured plasma levels of atrial natriuretic peptide (ANP) in 20 patients with impaired retinal circulation in order to monitor hypervolemic hemodilution. In 18 control subjects, plasma ANP levels averaged 37.4 +/- 7.3 pg/ml and 30.0 +/- 5.4 pg/ml before and after an i.v. infusion of 250 ml of HAES 6% over 3 hours. In 8 of 20 patients, plasma ANP exceeded the highest value of 87 pg/ml in the controls at the end of the first infusion. In the group B, ANP increased from 103 +/- 21.6 pg/ml to 142 +/- 12 pg/ml before and after the infusion. In the remaining 12 patients (group A), plasma levels of ANP were 41.1 +/- 8.6 and 44.8 +/- 6.3 pg/ml at the start and the end of the first infusion of HAES. All patients received 500 ml of HAES daily for 8 days. In group B, hemoglobin was significantly lower on day 8 (11.7 +/- 0.48 versus 13.2 +/- 0.38 mg/100 ml) compared to group A (p less than 0.005). Similarly, hematocrit and serum protein was reduced to a greater extent in group B compared to group A indicating intravascular volume expansion. Measuring plasma ANP-levels might be of value to identify patients with reduced tolerance to hemodilution therapy.

Aged↗
PubMed1991

[Cardiac peptides and their importance in heart failure].

Atrial natriuretic peptide (ANP) exhibits a favorable pharmacological profile in heart failure. In reduces preload and afterload by its natriuretic and vasodilatatory actions. Furthermore, it reduces the activity of the renin aldosterone system. This peptide is activated in early heart failure. Plasma levels of 1-28-hANP are elevated and they correlate with the clinical stage of heart failure, as well as with hemodynamic abnormalities. However, the efficacy of this cardiac hormone in heart failure is limited by renal resistance. Possible mechanisms are a reduced renal perfusion pressure, a receptor down-regulation or an overactivity of sodium-retaining hormones like the renin aldosterone system, and the sympathetic activity. The brain natriuretic peptide (BNP) is also stimulated in heart failure; however, its role in the pathophysiology of heart failure remains to be determined.

Animals↗
PubMed1991

[The effect of hemodynamic changes in 24-hour milrinone infusion on sympathetic activity and the renin-angiotensin-aldosterone system in patients with severe heart failure].

The hemodynamics of 18 patients (subgroup A) with severe heart failure (baseline Cl less than or equal to 1.55 l.min-1.m-2), including three patients with cardiogenic shock, and another 22 patients (subgroup B) with moderate heart failure (baseline Cl from 1.55 to 2.5 l.min-1.m-2) were investigated during a 24 h milrinone infusion, combined with investigation of the response of the sympathetic tone (plasma catecholamine levels) and the renin-angiotensin-aldosterone system to the hemodynamic improvement in both subgroups. Cl increased (p less than or equal to 0.001) to 162.7% after 5 min and further to 206.4% of baseline after 30 min of milrinone therapy in subgroup A, and in B to 139.3% and further to 146.4% after 15 min. PCWP decreased (p less than or equal to 0.001) to 83.8% and further to 65.5% of baseline after 30 min in subgroup A, and to 58.4% in subgroup B. Heart rate decreased (p less than or equal to 0.05) from 99.4 to 94.7 bpm in A and showed a decreasing tendency in B. MAP rose in A from 75.5 to 79.4 after 1 h and further to 83.3 mm Hg (p less than or equal to 0.01) after 24 h; in subgroup B, MAP did not change. Plasma noradrenaline level decreased (p less than or equal to 0.001) in A from 1419.5 (B: 782.9) to 838.2 (B: 529.6) after 1 h and further to 655.1 (B: 467.9) pg/ml after 24 h. Plasma renin decreased (p less than or equal to 0.01) in A from 1047.6 (B: 460.2) to 597.4 (B: 222.5) and further to 392.6 (B: 191.7) microU/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of androgen manipulations on chemically induced colonic tumours and on macroscopically normal colonic mucosa in male Sprague-Dawley rats.

Epidemiological and experimental studies suggest that androgens influence colonic carcinogenesis. We investigated the effects of hormonal manipulations (surgical and chemical castration, hormone substitution) on colonic tumour development, tumour and mucosal histopathology, and epithelial proliferation in macroscopically normal colonic mucosa in male rats, after induction of chemical colon carcinogenesis by subcutaneous injections of azoxymethane (AOM). Chemical castration with cyproterone acetate, but not surgical castration, resulted in increased colonic tumorigenesis, which was accompanied by decreased crypt length, decreased number of cells per crypt, and increased crypt epithelial mitotic index in the right colon. Chemically castrated rats also had crypt hyperplasia and increased numbers of dysplastic foci in the left colon which were not seen with surgical castration. By contrast, rats given testosterone after surgical castration showed decreased colonic tumorigenesis with an increased proportion of tumours in the left colon and lower percentage of tumours with invasion. The grossly normal mucosa of the testosterone-substituted castrated rats showed decreased crypt length in the right colon similar to the other groups of castrated rats, but no significant increase in mitotic index. Our results suggest that the anti-androgenic progestin cyproterone is a potent enhancer of colonic tumorigenesis and epithelial proliferative abnormalities after AOM administration. Exogenous testosterone after castration alters tumour distribution and characteristics and suppresses epithelial proliferative abnormalities. Finally, androgen effects on the colonic mucosa are more prominent in the right than in the left colon, suggesting different influences of hormones on the epithelium of these anatomical sites.

Adenocarcinoma↗