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Biomedical subjects

M Hamann

Publications and source records attributed to M Hamann.

At least 55 records · Page 3Linked to original sources
PubMed1994

Role of calcium ions in the pressure control of renin secretion from the kidneys.

In this study we examined the role of calcium ions in the control of renin release by the renal artery pressure. For this purpose renin secretion rates (RSR) were measured in isolated rat kidneys perfused at pressures of 140, 100, 80 and 40 mmHg (19, 13, 11, 5 kPa) with media containing either 1.5 mmol/l ("normal") or zero calcium concentrations (calcium-free perfusate with 0.5 mmol/l EGTA). At normal calcium the RSR was inversely related to the renal artery pressure, whereas calcium withdrawal resulted in an almost linear and proportional relationship between RSR and perfusion pressure. As a consequence, RSR at 140 mm Hg (19 kPa) with a calcium-free medium was similar to renin release at 40 mm Hg (5 kPa) with normal calcium. The nitric oxide (NO) donor sodium nitroprusside (1 mumol/l) stimulated RSR in a pressure-dependent fashion at a calcium concentration of 1.5 mmol/l. With a calcium-free perfusate, sodium nitroprusside did not restore the inverse pressure dependence of RSR seen with normal calcium but almost doubled the RSR across the whole pressure range. Whilst RSR was significantly reduced by angiotensin II (1 nmol/l) in the range between 40 mmHg and 140 mmHg (5-19 kPa) with normal calcium, withdrawal of extracellular calcium ions practically abolished the inhibitory action of angiotensin II. Since angiotensin II attenuated RSR especially at low renal perfusion pressure, our results indicate that renin release in this pressure range is still inhibitable by calcium mobilization in renal juxtaglomerular cells. Thus, the enhancement of renin secretion at lower pressures cannot be explained by a decreased sensitivity of renin release towards calcium ions.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1994

Role of the macula densa in the control of renal renin gene expression in two-kidney/one-clip rats.

This study was designed to examine whether macula densa function is involved in the changes of renal renin gene expression upon acute hypoperfusion of one kidney. To block macula densa function, rats with free access to salt and water were subcutaneously infused with furosemide (12 mg/day) for 6 days. Then, 4 days after the start of the infusion, the left renal arteries were clipped with 0.2-mm silver clips and renin mRNA levels in ipsilateral and contralateral kidneys, as well as plasma renin activities (PRA), were determined 48 h after clipping. In non-clipped animals furosemide increased PRA from 10 to 47 ng angiotensin I.h-1.ml-1 and raised renin mRNA levels in both kidneys 2.5-fold. In vehicle-infused animals, clipping of the left renal artery increased PRA to 37 ng angiotensin I.h-1.ml-1 and led to a 5-fold rise of renin mRNA levels in the ipsilateral kidneys and to a suppression to 20% of the control values in the contralateral kidneys. PRA values in clipped and furosemide-infused animals were 45 ng angiotensin I.h-1.ml-1. In these animals renin mRNA levels increased in the ipsilateral kidneys to similar absolute values as in vehicle-infused rats, whilst contralateral renin mRNA levels fell to about 25% of the respective controls. These findings indicate that the stimulations of renin gene expression by inhibition of macula densa salt transport and by renal artery clipping are not additive, suggesting that the macula densa mechanism may participate in the stimulation of renin gene expression upon hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1994

Endothelium derived relaxing factor is involved in the pressure control of renin gene expression in the kidney.

To study the influence of endothelium derived relaxing factor/nitric oxide (EDNO) on renin gene expression, the effects of a 2-day treatment with the NO-synthase inhibitor nitro-L-arginine-methylester (L-NAME, 40 mg/kg twice a day) on plasma renin activity (PRA) and renal and adrenal renin m-RNA levels were examined in conscious rats with and without unilateral renal clips (0.2 mm). In sham-clipped animals L-NAME led to a decrease of PRA from 7.5 to 2.5 ng angiotensin (ANGI).h-1.ml-1 and to a 35% decrease of renal renin m-RNA levels. Unilateral renal artery clipping increased PRA to 35 and to 13 ng ANGI.h-1.ml-1 in vehicle and in L-NAME-treated rats, respectively. In the clipped kidneys renin m-RNA levels increased to 450% of control values in vehicle-treated animals and to 220% of control values in L-NAME-treated animals. In the contralaterals as opposed to clipped kidneys, renin m-RNA levels decreased to 16% and 50% of the control values in vehicle- and in L-NAME-treated animals, respectively. In the adrenal glands renin m-RNA levels were not significantly changed either by clipping of one renal artery or by treatment of animals with L-NAME. The NO-donor sodium nitroprusside (100 microM) was found to increase renin secretion and renin m-RNA levels in primary cultures of renal juxtaglomerular cells. These findings suggest that EDNO is involved in the control of the renin gene by the renal perfusion pressure.

Amino Acid Oxidoreductases↗
PubMed1994

Renal autacoids are involved in the stimulation of renin gene expression by low perfusion pressure.

This study aimed to examine the role of local autacoids for the regulation of renin secretion and renin gene expression by the renal perfusion pressure. To this end the effects of unilateral reduction of renal perfusion by 0.2 mm clips on plasma renin activity and on renal renin mRNA levels were examined in rats treated with the cyclooxygenase inhibitor meclofenamate (8 mg/kg body wt, twice a day), with the NO-synthase inhibitor nitro-L-arginine-methylester (L-NAME, 40 mg/kg body wt, twice a day) or with a combination of both. L-NAME alone decreased basal PRA values from 9.9 to 5.4 ng Ang I/hr x ml, while meclofenamate alone and the combination meclofenamate/L-NAME had no consistent effect on basal PRA. Unilateral renal artery clipping increased PRA values from 9.9 ng Ang I/hr x ml to 34, 27, and 16 ng Ang I/hr x ml in vehicle, meclofenamate, and L-NAME treated animals, respectively, but did not increase PRA in meclofenamate/L-NAME treated rats (9.5 ng Ang I/hr x ml). Renal renin mRNA levels in the clipped kidneys increased 4.8-, 2.6-, 2.5- and 1.8-fold in the clipped kidneys in vehicle, meclofenamate, L-NAME and meclofenamate/L-NAME injected animals, respectively. These findings indicate that both the inhibition of prostaglandin synthesis and of the formation of endothelium-derived relaxing factor (EDRF) attenuate the increase of renin gene expression and of renin secretion in response to acute unilateral renal hypoperfusion and that the effects of both maneuvers are additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Hemophiliac arthropathy of the knee joint. Gd-DTPA-enhanced MRI; clinical and roentgenological correlation].

17 patients with hemophilic arthropathy of the knee joint were studied with static and dynamic MRT before and after i.v. bolus injection of Gadolinium-DTPA (0.1 mmol/kg body weight). After contrast enhancement, synovial proliferations exhibited an increase of signal intensity (SI) on FFE and SE images of 47.7% and 37.4% respectively, whereas muscle and fatty tissue, tendons, bone marrow and joint effusion revealed only minor increase in SI. The gradient of signal intensity (ratio SI/time) of pannus was 39.6%/min. Gd-DTPA enhanced MRI studies delineate and quantify the synovial proliferations in hemophilic arthropathy. Dynamic studies in hemophilic arthropathy do not provide qualitative assessment of the inflammatory process.

Adult↗
PubMed1994

[The nitinol stent as a palliative measure in inoperable carcinoma of the esophagus and cardia. Possibilities and limitations of the procedure].

Nitinol stents were used in ten patients as palliative treatment for carcinoma of the esophagus and the cardia. Following insertion of the stent the severity of dysphagia decreased on average from 3.2 to 1.5 (on a scale from 0-4). Difficulties with stent opening and passage through the gut were found particularly in the region of metal sutures at esophago-jejunal anastomoses. One stent, which had been obstructed by mucosal folds, had to be removed and replaced. One stent which had been incorrectly placed was extended by introducing a second stent by a coaxial technique. During the period of observation, six patients died after an average of 4.6 months. The palliative effect of the stent lasted on average for eleven weeks. In two patients the tumour grew beyond the stent and in three there was tumour growth into the stent.

Adenocarcinoma↗
PubMed1994

Differential effects of extracellular anions on renin secretion from isolated perfused rat kidneys.

We investigated the relevance of anions for the regulation of renin secretion from the kidneys. For this purpose we measured renin release from isolated rat kidneys that were perfused with medium containing either 120 mmol/l (normal) chloride or 95 mmol/l of isethionate, acetate, or nitrate anions in exchange for equimolar amounts of chloride. Lowering the extracellular chloride concentration by either of these maneuvers significantly enhanced renin secretion rates (RSR) at a perfusion pressure of 100 mmHg. Increasing pressure above 100 mmHg inhibited renin release in the presence of isethionate and acetate but not with nitrate anions. The renin stimulatory effects of isethionate and acetate but not that of nitrate anions disappeared in the presence of bumetanide (100 mumol/l), an inhibitor of macula densa chloride transport. Activation of renin secretion by isethionate and acetate was blunted with 100 pmol/l angiotensin II (ANG II), whereas tenfold higher concentrations of ANG II were required to attenuate the effect of nitrate ions. The amount of renin released in the presence of nitrate was fully additive to RSR values obtained with maximally effective doses of isoproterenol. These findings are consistent with the idea that impermeant anions such as isethionate and acetate enhance renin secretion from the kidneys predominantly via the tubular macula densa mechanism. The stimulatory influence of membrane-permeable nitrate anions appears to involve additional pathways and is mediated by a decreased calcium sensitivity of the renin secretory process rather than resulting from an adenosine 3',5'-cyclic monophosphate-dependent action.

Acetates↗
PubMed1994

Interrelation between renin mRNA levels, renin secretion, and blood pressure in two-kidney, one clip rats.

To examine the interrelation between renin mRNA levels, renin secretion, and blood pressure in rats, we clipped the left renal arteries of rats and measured renin mRNA levels in both kidneys, plasma renin activity, and blood pressure. One and 2 days after clipping, renin mRNA levels increased 3-fold and 4.3-fold in the stenosed kidney and were suppressed to 52% and 26% of controls in the intact kidneys; plasma renin activity increased from 8 to 16.5 and to 30.5 ng angiotensin I.h-1.mL-1 and systolic blood pressure rose from 114 to 123 and to 137 mm Hg. We found a strong correlation (P < .001) between plasma renin activity and renin mRNA levels in the clipped kidneys. We also found significant correlations (P < .05) between mRNA levels in the clipped and intact kidneys and between plasma renin activity and blood pressure for the individual animals. Treatment of normal rats with the converting enzyme inhibitor ramipril (5 mg/kg twice a day) for 2 days increased renin mRNA levels in both kidneys fourfold. In animals with unilateral clips, additional treatment with ramipril increased renin mRNA levels 6.4-fold in the stenosed and 3.3-fold in the intact kidneys. These findings suggest that endogenous angiotensin II exerts an inhibitory effect on renin mRNA expression in normal kidneys, clipped kidneys, and their contralaterals. Suppression of the renin gene in contralateral kidneys seems not to be directly mediated by the rise of plasma renin activity or by the rise of blood pressure in two-kidney, one clip rats.

Angiotensin II↗
PubMed1993

Purification of human muscle satellite cells by flow cytometry.

To purify satellite cells directly from human muscle biopsies, we have developed a method based on size separation of dissociated cells by flow cytometry. Immediately after tryptic dissociation of human muscle biopsies and elimination of erythrocytes, microscopic observation and flow cytometry analysis of cell suspensions revealed two populations of cells differing in size and nucleocytoplasmic ratio. Clonal cultures of these two cell types with a manual procedure demonstrated that only the small cells were myogenic satellite cells. Flow cytometry-sorting and analysis of the small cell population showed that (1) all sorted cells contained desmin immediately after dissociation and plating; (2) more than 98% of the cells expressed the 5.1.H11 epitope after 2 weeks of proliferation in culture; and (3) 90% of the sorted cells were able to form myotubes when cultivated at low density or in clonal cultures. Thus, human muscle satellite cells can be directly purified from human muscle samples using flow cytometry.

Adolescent↗
PubMed1993

Which factor mediates reno-renal control of renin gene expression?

OBJECTIVE: To obtain information about possible pathways mediating the suppression of renin gene expression in the contralateral kidneys of stenosed kidneys. DESIGN: The effects of unilateral renal denervation and of treatment with an angiotensin II antagonist (losartan) on renal renin gene expression were examined in a two-kidney, one-clip model. METHODS: Renal renin messenger RNA levels, plasma renin activity, blood pressure and kidney weights were monitored over 10 days in adult male Sprague-Dawley rats with various unilateral reductions of renal blood flow achieved with silver clips of 0.2, 0.3 and 0.4 mm inner diameter. RESULTS: With all the clip sizes used, renin messenger RNA levels increased transiently in the clipped kidneys, the time course and the magnitude of the increase being dependent on the degree of flow reduction. In the contralateral kidneys clipping caused sustained decreases in renin messenger RNA to levels proportional to the clip size. The suppression of renin gene expression in the contralateral kidneys was not related to compensatory growth of the organs nor to changes in plasma renin activity or arterial pressure. Unilateral denervation of the kidney before clipping had no influence on the characteristic increase and decrease in renin messenger RNA in the stenosed and contralateral kidneys, respectively. Treatment of the rats with losartan led to fourfold increases in renal renin messenger RNA levels and to sixfold increases in plasma renin activity in control rats. A 0.3-mm clip did not further increase renin messenger RNA or plasma renin activity in losartan-treated rats but again led to suppression of renin messenger RNA in the contralateral kidney to 50% of the levels found in the clipped kidneys. CONCLUSIONS: The results suggest that the suppression of renin gene expression in the contralateral kidneys of stenosed kidneys is not due to compensatory renal growth nor mediated by systemic blood pressure, angiotensin II AT1 receptors or renal nerves. We therefore hypothesize that kidneys with reduced perfusion release a humoral factor that acts as a potent inhibitor of renin gene expression.

Angiotensin Receptor Antagonists↗
PubMed1993

A voltage-dependent proton current in cultured human skeletal muscle myotubes.

1. A voltage-dependent proton current, IH, was studied in cultured myotubes obtained from biopsies of human muscle, using whole-cell recording with the patch-clamp technique. 2. With a pHo of 8.0 and a calculated pHi of 6.3, IH was activated at voltages more depolarized than -50 mV and its conductance reached its maximum value at voltages more depolarized than +10 mV. 3. Studies of the reversal potential of IH during substitution of K+, Na+, Ca2+, Cl-, Cs+ and H+ in the extracellular solution indicated that protons were the major charge carriers of IH. 4. IH was also activated during a voltage step to +22 mV with a pHo of 7.3 and a calculated pHi of 7.3. 5. Acidification of the extracellular solution led to a shift towards depolarized voltages of the conductance-voltage relationship. 6. Stationary noise analysis of IH suggested that the elementary event underlying IH was very small with a conductance of less than 0.09 pS. 7. Extracellular application of various divalent cations blocked IH. The block by divalent cations was voltage dependent, being more efficient at hyperpolarized than at depolarized voltages. For Cd2+, the Michaelis-Menten constant (Km) for the block was 0.6 microM at -28 mV and 10.4 microM at +12 mV. 8. Ca2+ was a less efficient blocker than Cd2+ but could block IH at physiological concentrations (the Km values for the block were 0.9 mM at -38 mV and 7.3 mM at -8 mV). 9. The voltage-dependent properties of IH and its ability to be affected by pH and Ca2+ suggest that IH might be used by skeletal muscle cells to extrude protons during action potentials. 10. A model of IH activation suggests that under extreme conditions, the conductance of IH can reach 40% of its maximum value after less than ten action potentials.

Action Potentials↗
PubMed1993

Increased plasma viscosity as a reason for inappropriate erythropoietin formation.

The aim of this study was to examine whether altered plasma viscosity could contribute to the inappropriately low production rate of erythropoietin (EPO) observed in patients suffering from hypergammaglobulinemias associated with multiple myeloma or Waldenström's disease. We found that the EPO formation in response to anemia in these patients was inversely related to plasma viscosity. A similar inverse relationship between plasma viscosity and EPO production was seen in rats in which EPO formation had been stimulated by exchange transfusion and the plasma viscosity of which was thereby altered by using exchange solutions of different composition to alter plasma viscosity and thus whole blood viscosity independently from hematocrit. Raising the gammaglobulin concentration to approximately 40 mg/ml plasma in the rats almost totally blunted the rise in serum EPO levels despite a fall of the hematocrit to 20%. Determination of renal EPO mRNA levels by RNase protection revealed that the reductions in serum EPO levels at higher plasma viscosities were paralleled by reductions in renal EPO mRNA levels. Taken together, our findings suggest that plasma viscosity may be a significant inhibitory modulator of anemia-induced EPO formation. The increased plasma viscosity in patients with hypergammaglobulinemias may therefore contribute to the inappropriate EPO production, which is a major reason for the anemia developing in these patients.

Adult↗
PubMed1990

Electrophysiological study of tert-butylbicyclophosphorothionate-induced block of spontaneous chloride channels.

The action of TBPS (tert-butylbicyclophosphorothionate) on spontaneous chloride channels recorded from porcine pars intermediate lobe cells in primary culture has been studied. This compound, which binds specifically to the gamma-aminobutyric acidA (GABAA) receptor complex, is known as a channel-gating (non-competitive) GABA antagonist. The present results show that TBPS reduces spontaneous chloride channel activity in a dose-dependent manner, with an IC50 equal to 55 nM, which is a value comparable to its affinity for the GABAA binding sites. Single-channel analysis revealed that TBPS affects neither the amplitude nor the open time of these spontaneous channels but prolongs the longer closed times, resulting in a dramatic decrease in opening probability.

Animals↗
PubMed1988

Quantitative evaluation of the properties of a pyridazinyl GABA derivative (SR 95531) as a GABAA competitive antagonist. An electrophysiological approach.

We have investigated the effects of an aryl-aminopyridazine derivative of GABA (SR 95531) on dose-response curves of GABA-induced depolarizations from dorsal root ganglion neurones recorded intracellularly. The reversible shift to the right of the dose-response curves in a parallel fashion and the dissociation constant (KB) value of 0.13 +/- 0.02 microM (n = 15) indicate that this compound is a potent competitive GABAA antagonist. The competitive nature of SR 95531-induced antagonism was confirmed by single channel analysis. In excised membrane patches from bovine chromaffin cells (outside out configuration), 0.2-0.5 microM SR 95531 did not alter the mean open time of GABA-activated channels and did not introduce further short closing gaps within bursts. Whole cell recordings from cultured nodose ganglion neurones indicated that SR 95531 (10 microM) did not modify significantly any of the 3 types of calcium currents already reported in sensory neurones. This result might be of importance for further studies of presynaptic GABA actions on transmitter release.

Adrenal Medulla↗
PubMed1987

Monooxygenase induction by various xenobiotics and its influence on rat liver microsomal metabolism of chrysene in comparison to benz[a]anthracene.

The potencies of various xenobiotics for induction of monooxygenases and their influence on the rat liver microsomal metabolite profile of the environmentally relevant weak carcinogen, chrysene, was determined. Among the widely distributed chemicals, polychlorinated biphenyls (PCB) and preferentially 3,3',4,4'-tetrachlorobiphenyl as well as PAHs and their heterocyclic analogues such as benzo[a]pyrene, benzo[b]- and -[j]fluoranthene, indeno[1,2,3-cd]pyrene, dibenz[a,h]acridine, benzo[b]naphtho-[2,1-d]thiophene, and 5,6-benzoflavone were found to be potent inducers stimulating the formation of the proximate, and some of them also the ultimate carcinogen of chrysene. Lindane, carbaryl, DDT, and pentachlorophenol were found to be inefficient or weak inducers. With the exception of phenobarbital no inducers were found among the pharmaceuticals investigated. Sex-dependent metabolism was found for Wistar-rats. No 1,2-oxidation was observed in females, and turnover rates were lower than in males. These findings confirm the results previously obtained with benz[a]anthracene as substrate. The inducing potencies of various compounds tested were similar for both of these substrates. It is interesting to note that in most cases the same effective xenobiotic induces the bay-region diolepoxide in both, chrysene and benz[a]anthracene.

Animals↗
PubMed1987

Electrophysiological study of SR 42641, a novel aminopyridazine derivative of GABA: antagonist properties and receptor selectivity of GABAA versus GABAB responses.

A new arylamino-pyridazine gamma-aminobutyric acid (GABA) derivative, SR 42641, has been tested for its ability to antagonize the actions of GABA on mammalian sensory neurones. SR 42641 and bicuculline reversibly decreased GABAA-induced depolarizations and currents recorded intracellularly from dorsal root ganglion neurons (DRG). Dose-response curves were shifted to the right in a parallel fashion. KB values (determined under voltage clamp conditions) were respectively 0.12 +/- 0.05 and 0.38 +/- 0.08 microM. Similar values were obtained with current clamp recording conditions. The study of the GABA-induced Cl- current under voltage-clamp conditions did not show any voltage-dependency of the antagonist effect of SR 42641. In nodose ganglion neurones, SR 42641 (0.4-4.5 microM) did not alter the (-)-baclofen-induced shortening of the calcium component of action potentials. At concentrations higher than 10 microM, SR 42641 itself prolonged calcium-dependent action potentials. Patch-clamp recordings from DRG cultured neurones indicated that SR 42641 did not affect the calcium current responsible for sustained calcium entry into cells. We conclude that SR 42641 is a potent competitive GABA antagonist, specific for the GABAA receptor. It does not act at the level of the chloride ionophore.

Animals↗
PubMed1985

Monooxygenase induction by various xenobiotics and its influence on the rat liver microsomal metabolite profile of benz[a]anthracene.

Several pesticides (lindane, carbaryl, pentachlorophenol, DDT), polycyclic aromatic hydrocarbons (PAH) and heterocyclic analogues (fluoranthene, dibenz[a,h]anthracene, dibenz[a,h]acridine, indeno[1,2,3-cd]pyrene, 10-azabenzo[a]pyrene) and pharmaceuticals (diphenylhydantoin, ethinylestradiol, levonorgestrel) were tested for their potencies to induce monooxygenase activities in the rat liver by means of recording the metabolite profile of benz[a]anthracene in rat liver microsomal incubations. Some of them were found to be weak or moderate inducers, but even less efficient ones altered the benz[a]anthracene metabolite profile significantly. Only indeno [1,2,3-cd]pyrene stimulated the bay-region oxidation of benz[a]anthracene. A sex-dependent metabolism was observed in both untreated and contraceptive-pretreated Wistar rats.

Animals↗