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Biomedical subjects

B Hesse

Publications and source records attributed to B Hesse.

At least 91 records · Page 5Linked to original sources

Haemodynamic and humoral effects of lower body negative pressure in normal, sodium-replete man during angiotensin-converting enzyme inhibition with captopril.

The significance of the renin-angiotensin system (RAS) for circulatory homeostasis during gravitational stress (10 min of lower body negative pressure, LBNP, at -40 mmHg) was investigated in eight men on liberal sodium intake. The function of RAS was inhibited by a single oral dose of 100 mg captopril, an angiotensin-converting enzyme inhibitor. Plasma concentrations of renin and angiotensin I were normal before and increased after captopril and during LBNP. Plasma concentration of angiotensin II was normal before captopril, increased during LBNP, and fell to low values after captopril. Systolic blood pressure decreased more during LBNP after captopril than in the control situation. In three cases, the LBNP experiment after captopril had to be interrupted due to marked hypotension. Heart rate and plasma concentration of adrenaline increased above pre-captopril levels. In six subjects, plasma concentration of noradrenaline increased more during LBNP after captopril, less in two subjects, whereas the arginine vasopressin concentration increased more after captopril in all five subjects where measurements were available. The results demonstrate that RAS participates in blood pressure homeostasis also in sodium-replete, normal man. The enhanced increases in heart rate and plasma catecholamines after captopril do not suggest that sympathetic reflex activity during gravitational stress is blunted after captopril, in contrast to the evidence from animal experiments.

Adult↗

The influence of the renin-angiotensin system on adrenergic vasoconstrictor responses in the forearm and splanchnic region in sodium deplete man.

In sodium deplete subjects forearm (FBF) and splanchnic (SBF) blood flows were measured at rest and during lower body negative pressure (LBNP) before and during angiotensin II (ANG II) blockade. Both FBF and SBF were reduced by LBNP. Forearm blood flow and forearm vascular resistance were unaffected by ANG II blockade (intra-arterial saralasin, n = 6; i.v. enalapril, n = 9) both at rest and during LBNP. In contrast, resting SBF increased and splanchnic vascular resistance decreased after i.v. enalapril (n = 10). The low resistance was completely unchanged during the following LBNP. It is concluded that acute ANG II blockade has no influence on the vascular resistance in the human forearm, but increases basal SBF in sodium depleted subjects and 'paralyses' the vasoconstrictor response to LBNP.

Angiotensin II↗

Effects of antimalarial drugs on phospholipase A and lysophospholipase activities in plasma membrane, mitochondrial, microsomal and cytosolic subcellular fractions of rat liver.

Activities of membrane-associated phospholipases A1 and A2, and membrane-associated as well as soluble lysophospholipases were measured in different subcellular fractions of rat liver, using suspensions of stereospecifically labelled radioactive phospholipids as substrates. Plasma membranes and endoplasmic reticulum were shown to contain phospholipase A1 and lysophospholipase activities, both of which could be stimulated by Ca2+, mitochondria Ca2+-dependent phospholipase A2 and cytosol Ca2+-independent lysophospholipase activities. Each of these lipolytic enzymes could be inhibited by antimalarial drugs (chloroquine, mepacrine, primaquine) at concentrations above 1 x 10(-4) M. Inhibition of the alkaline cytosolic lysophospholipase by these drugs was noncompetitive with respect to the substrate, and the inhibitory potency increased, when the pH was raised.

Animals↗

Urinary excretion of kallikrein before and after operation for aldosterone-producing adenoma.

Urinary kallikrein excretion (UKal), determined by the esterase method, was measured in 10 normotensive volunteers, 10 patients with essential hypertension and in 7 patients with primary aldosteronism before and after operative removal of the adenoma. UKal values were low in 5 of the patients with essential hypertension. Preoperative UKal values in the patients with aldosteronism did not differ significantly from those of the normal subjects, but decreased in all after operation in parallel with changes in urinary excretion of tetrahydroaldosterone and plasma aldosterone concentration. The study supports the assumption of an association between the renal kallikrein-kinin system and the mineralocorticoid state in man.

Adenoma↗

Decrease in beta-receptor density explaining the development of pindolol- and prenalterol-tolerance in orthostatic hypotension.

A 58-year-old woman with diabetic autonomic dysfunction was well treated for orthostatic hypotension with pindolol. After eight months however, symptoms recurred in spite of continued treatment with pindolol. Addition of prenalterol, a beta-blocking agent with very high intrinsic sympathomimetic activity, had a marked clinical effect on her orthostatic hypotension. Before treatment with prenalterol, stroke volume and left ventricular enddiastolic volume markedly decreased during tilt, as demonstrated by radionuclide angiography. After short-term prenalterol treatment, the orthostatic decreases of stroke volume and left ventricular end-diastolic volume were less pronounced. During continued prenalterol treatment, both symptoms and haemodynamic changes recurred in the erect position. Beta-receptor density in her lymphocytes decreased from elevated levels before prenalterol to subnormal levels, when the clinical effect had disappeared. The data suggest that the tolerance development to prenalterol may be explained by the decrease in beta-adrenergic receptor density.

Adrenergic beta-Agonists↗

A combined assay of three lysosomal marker enzymes: acid phosphatase, beta-D-glucuronidase, and beta-N-acetyl-D-hexosaminidase.

A simplified and rapid method for simultaneous activity measurements of three lysosomal marker enzymes, acid phosphatase, beta-glucuronidase, and beta-N-acetyl-D-hexosaminidase is described. The incubation is carried out in a single test tube and stopped by adding an alkaline sodium dodecyl sulfate solution, thus avoiding centrifugations and allowing for higher Triton X-100 concentrations in the incubation media. Two products of the beta-glycosidases (phenolphthalein and 2-nitrophenolate) are measured spectrophotometrically at the respective wavelengths (555 and 420 nm), and one of the acid phosphatase products is quantitatively determined by measuring inorganic phosphate.

Acid Phosphatase↗

Spontaneous tumors and lifespan of female NMRI mice of the outbred stock Sut:NMRT during a lifetime study.

A group of 150 female NMRI mice of the outbred stock Sut:NMRT was kept until they died naturally, at which time they were necropsied and examined histologically for spontaneous tumors. The natural life expectancy (median) was 782 days. Life expectancy was markedly reduced by mammary and pulmonary adenocarcinoma, and by tumors of the hypophysis. The spontaneous tumor rate was 58%. That is to say, 87 of the 150 mice had spontaneous tumors: 57 animals each had one tumor, 20 animals each had two tumors, and 10 animals each had three tumors. The organs most commonly affected by tumors were those of the lymphoreticular and haematopoietic systems, followed by the respiratory tract in second place and the breast in third place. Data reported in the literature generally show the same organ distribution, but the total tumor rate given is generally somewhat lower as the animals are seldom left alive until they die naturally (spontaneously).

Aging↗

Dose-response relationship in normal subjects of prenalterol, a beta-adrenergic agonist with positive inotropic and resistance lowering effects.

The acute haemodynamic effects of increasing doses of parenterally administered prenalterol-a beta-adrenergic stimulating drug-were assessed in normal subjects by means of radionuclide ventriculography. Prenalterol induced dose-related increases in the left ventricular ejection fraction and the systolic pressure end-systolic volume ratio. Left ventricular end-systolic and end-diastolic volumes decreased to the same extent accounting for an unchanged stroke volume. Cardiac output increased due to a rise in the heart rate. Systolic blood pressure increased, whereas diastolic and mean blood pressure remained unchanged. Calculated total peripheral resistance decreased significantly. The maximum effect of prenalterol on cardiac performance occurred with a dose of 18 to 36 micrograms/kg. Plasma concentrations of prenalterol showed large interindividual variations. In conclusion, prenalterol improves the pump function of the normal heart and causes a fall in peripheral vascular resistance, implying a reduction of the load on the heart. These effects may prove beneficial in the treatment of acute heart failure.

Adrenergic beta-Agonists↗

Effects of the serine protease inhibitor gabexate mesilate on purified pancreatic phospholipase A2.

The catalytic activity of purified porcine pancreatic phospholipase A2 is competitively inhibited by the cationic amphiphilic serine protease inhibitor gabexate mesilate (ethyl 4-(6-guanidinohexanoyloxy) benzoate methanesulfonate). A Ki of 1.3 X 10(-4)M was found when 1,2-dioctanoyl-sn-glycero-3-phosphorylcholine was used as a substrate. The main metabolites of this drug, 6-guanidinocaproic acid and ethyl p-hydroxy-benzoate, had no effect in concentrations up to 10(-2)M. From the high gabexate mesilate concentrations required to reduce phospholipase A2 activity and from the considerably lower drug concentrations sufficient to cause beneficial effects in acute pancreatitis it is concluded that direct inhibition of pancreatic phospholipase A2 cannot be the cause of the therapeutic results, improvement of the symptoms and prognosis of acute pancreatitis.

Animals↗

A spontaneous transplantable lymphosarcoma of the Syrian golden hamster (Mesocricetus auratus): Experimental induction of metastases after subcutaneous and intravenous inoculation.

A spontaneously occurring lymphosarcoma of the Syrian golden hamster was both subcutaneously and intravenously inoculated into 300 female and male animals each. Tumor growth was observed at a 100% rate. Using both types of inoculations, metastases occurred in 50% of the inoculated animals, preferentially in lungs, liver, pancreatic lymph nodes, spleen and kidney. The participation of different lymph node groups was more frequent after subcutaneous application. The transplantable tumor described might serve as a mode for additional studies on experimentally induced metastasis.

Animals↗

Skin tumor formation in the European hamster (Cricetus cricetus L.) after topical initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA).

Initiation with the carcinogen 7,12-dimethylbenz[a]anthracene followed by promotion with the hyperplasiogenic phorbol ester 12-O-tetradecanoylphorbol-13-acetate carried out on the dorsal skin of European hamsters (Cricetus cricetus L.) led to the formation of a broad spectrum of skin tumors in terms of a two-stage principle. Tumor formation involved the epidermis and its appendages, the connective tissue, and the vascular and pigmentary system. With regard to the sensitivity to initiation with DMBA alone and initiation with DMBA and promotion with TPA the European hamster occupies a special position since all of the DMBA-TPA sensitive two-stage target organs known from the mouse, rabbit, Syrian golden hamster and rat are combined in this animal.

9,10-Dimethyl-1,2-benzanthracene↗

Evaluation of intravenous radionuclide angiography in detection of occlusive disease of the iliac arteries.

Radionuclide angiography (angioscintigraphy) of the iliac arteries was performed in 173 patients consecutively referred for arterial insufficiency of the legs. In 83 of the patients femoral angiography was also performed. The interobserver variation was evaluated by the agreement indices, kappa (K) and weighted kappa (Kw). For angiography the interobserver agreement was high (K and Kw 0.65 and 0.77 respectively). For angioscintigraphy the agreement between observers was fair (K = 0.52, Kw = 0.68), and equal to the intraobserver agreement (K = 0.55, Kw = 0.65). The comparison between angioscintigraphy and angiography gave K-values of 0.22-0.31 and Kw-values of 0.37-0.48. The nosographic sensitivity of angioscintigraphy was 61%, the nosographic specificity was 93%, and the predictive value for both a positive and a negative test was 83%. The prevalence of occlusion or severe stenosis was 34%. Inguinal pulse palpation detected 48% of iliac occlusions. It is concluded that the reliability of angioscintigraphy in the diagnosis of iliac arterial occlusive disease is acceptable for a non-invasive, rapid, inexpensive and widely available screening procedure. Although anatomical details are not visualized the information obtained is useful for the detailed planning and choice of subsequent diagnostic and therapeutic procedures. The method is well suited for repeat studies and may be modified to include the femoral arteries.

Adult↗

The influence of ACE-inhibition by captopril on renal formation and metabolism of angiotensins I and II in patients with renovascular hypertension.

Fourteen patients with hypertension of presumed renovascular etiology were studied by renal vein catheterization. Unilateral renin secretion was found in 8 patients. In 4 of these patients a positive veno-arterial difference of plasma angiotensin I concentration (PAI) across the affected kidney increased markedly after a single dose of captopril. Across the contralateral kidney the net veno-arterial PAI difference changed from about zero before captopril to clearly negative values after captopril. The PAI values in the remaining 4 patients, who were already on captopril before the catheterization, were similar to those observed after a single dose of captopril. In patients with bilateral renin secretion the renal veno-arterial PAI differences across the kidneys were positive or close to zero before captopril. After captopril both positive and negative veno-arterial differences of PAI were observed. The plasma angiotensin II concentrations decreased after captopril to low values. These low values together with extremely high PAI values demonstrate effective ACE-inhibition. A high generation rate of angiotensin I in the affected kidney in patients with unilateral renin secretion after captopril is probably explained by activation of the local renin secretion. The angiotensin I "consumption" in the contralateral kidney after captopril in spite of no angiotensin II formation suggests the presence of alternative degradation processes for angiotensin I in the human kidney.

Adult↗

Haemodynamic and clinical effects of isosorbide-dinitrate in patients with severe effort angina on beta-blocking treatment.

The effect of isosorbide-dinitrate (ISDN) 20 mg 4 times daily against placebo has been tested in 12 patients with stable effort induced angina pectoris receiving prophylactic treatment with metoprolol. ISDN did not decrease the attack rate or nitroglycerine consumption, nor was exercise tolerance increased after it. Left ventricular function, assessed by radionuclide ventriculography, increased in 6 out of 8 patients (p less than 0.1). It is concluded that ISDN has no place in the treatment of haemodynamically intact patients with severe angina pectoris in spite of beta-blocking treatment, but that it may be of value in the treatment of patients with left ventricular failure, including those whose left ventricular failure has been brought about by beta-blocking treatment necessitated by angina pectoris.

Adult↗