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Biomedical subjects

V Oberhauser

Publications and source records attributed to V Oberhauser.

17 recordsLinked to original sources
PubMed2001

Acetylcholine release in human heart atrium: influence of muscarinic autoreceptors, diabetes, and age.

BACKGROUND: An imbalance of sympathetic and parasympathetic drive to the heart is an important risk factor for cardiac death in patients with coronary heart disease, diabetes, and renal insufficiency. The amount of neurotransmitter released from peripheral autonomic nerves is modulated by presynaptic receptor systems. In analogy to alpha-autoreceptors on sympathetic nerves, muscarinic autoreceptors activated by endogenous acetylcholine may exist on parasympathetic nerves in the human heart. METHODS AND RESULTS: We developed a technique to study acetylcholine release from human atria and investigated muscarinic autoreceptor function. A pharmacological and molecular approach was used to characterize the subtype involved. Of the 5 muscarinic receptor subtypes cloned, only mRNA encoding for M(2)- and M(3)-receptors were detected. Potencies of several muscarinic antagonists against the release-inhibiting effect of the nonselective muscarinic agonist carbachol at the cardiac autoreceptor were correlated with published data for human cloned M(1)- through M(5)-receptors. CONCLUSIONS: This analysis clearly indicates that acetylcholine release in human atria is controlled by muscarinic M(2)-receptors. Blockade of these receptors by atropine doubles the amount of acetylcholine released at a stimulation frequency of 5 Hz. In atria of patients >70 years of age and patients with late diabetic complications, acetylcholine release is reduced. Locally impaired cardiac acetylcholine release may therefore represent a pathophysiological link to sudden cardiac death in elderly and diabetic patients.

Acetylcholine↗
PubMed2001

Contractile effects of tacrolimus in human and rat isolated renal arteries.

1. We tested the vasoactive properties of the immunosuppressive drug FK 506 (tacrolimus) in preconstricted rat and human isolated renal arteries in vitro. 2. In rat renal arteries, tacrolimus (3, 10 microM) showed a direct and dose-dependent contractile effect by maximally 23 microm (10% of the noradrenaline effect), which was only observed in the presence of intact endothelium. Moreover, a lower concentration of tacrolimus (1 microM) potentiated pressor responses to the sympathetic neurotransmitter noradrenaline but not to ATP in this species. ATP- (0.01-10 microM) induced vasodilation was not affected by tacrolimus (1 microM). 3. In contrast, in human interlobar arteries, tacrolimus failed to induce direct vasoconstriction and did not significantly potentiate constrictor responses to noradrenaline. Acetylcholine-(1 microM) induced vasodilation was much smaller in human than in rat renal arteries suggesting the lack of functional endothelium in the human preparation. 4. The findings suggest that tacrolimus releases an endothelium-derived constricting factor in rat renal arteries to increase vascular tone and to potentiate pressor responses to noradrenaline. In human interlobar arteries, this effect of tacrolimus is not observed probably because of the absence of functional endothelium or the necessary mediator mechanism.

Acetylcholine↗
PubMed2000

Dihydropyridine calcium antagonists and renal function in hypertensive kidney transplant recipients.

OBJECTIVE: To investigate whether calcium antagonists are nephroprotective in hypertensive cyclosporine-treated renal allograft recipients. METHODS: We studied 50 hypertensive and 17 normotensive renal transplants (eight females, nine males; 14-54 years, mean age 38.8 +/- 3.5 years). Hypertensive patients were randomized to be treated with (+Ca; 11 females, 13 males; 20-65 years, mean age 43.1 +/- 3 years) or without (-Ca; 15 females, 11 males; 25-60 years, mean age 41.3 +/- 2.5 years) a calcium antagonist (nitrendipine or nifedipine). Additional antihypertensives were given stepwise according to a standardized protocol: beta1-adrenoceptor blocker, diuretic alpha1-adrenoceptor blocker or vasodilator. Data were analysed at 0, 1, 2 and 3 years on an intention-to-treat basis. RESULTS: Hypertensive patients had a higher body mass index at 0/3 years (23.7 +/- 0.6/25.1 +/- 0.6 kg/m2) than normotensive patients (22.2 +/- 0.6/22.1 +/- 0.7 kg/m2). During the study, blood pressure in normotensive transplants was always slightly, but not significantly, lower than that of transplants with treated hypertension. There was no difference between the groups (+Ca) and (-Ca). Cr51-ethylenediaminetetracetic acid (EDTA) clearance (0/2 years) was 58 +/- 4/57 +/- 6 ml/min in normotensives, 52 +/- 4/47 +/- 4 ml/min in hypertensives (+Ca) and 47 +/- 4/49 +/- 6 ml/min in hypertensives (-Ca). Proteinuria (0/3 years) was 0.16 +/- 0.04/0.15 +/- 0.02 g/24 h in normotensive, 0.26 +/- 0.08/0.23 +/- 0.05 g/24 h in hypertensives (+Ca) and 0.26 +/- 0.07/0.22 +/- 0.05 g/24 h in hypertensives (-Ca). CONCLUSIONS: Post-transplant hypertension is associated with higher body mass index and poor renal function. No difference in the course of Cr51-EDTA clearance, serum creatinine, proteinuria or blood pressure was observed between groups treated with or without calcium antagonists. Calcium antagonists and conventional antihypertensive treatment have the same nephroprotective effect in hypertensive renal transplants, when treatment is started 3 months after transplantation.

Adult↗
PubMed1999

[Chronic renal failure--taming the sympathetic nervous system! New approach to delaying progression].

Previous research in end stage renal failure has focused on the renin-angiotensin-system. Today, we know, that in chronic renal failure sympathetic overactivity plays a pivotal role for progression of the disease and overall prognosis. The unique finding is that the damaged kidneys send afferent nerve impulses to the central nervous system to increase efferent sympathetic discharge. Systemically this sympathetic overactivity contributes to hypertension and associated cardiovascular complications. Locally in the kidney neurotransmitter release is enhanced, which induces proliferation thereby promoting loss of renal function. Consequently, it has been shown that pharmacological inhibition of sympathetic nerve activity prevents glomerulosclerosis and ameliorates proteinuria in models of chronic renal failure. Thus, the pathomechanism of sympathetic overactivity is likely to open a new therapeutic avenue for the treatment of hypertensive chronic renal failure patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Adenosine mediates nitric-oxide-independent renal vasodilation by activation of A2A receptors.

OBJECTIVE: Adenosine dilates rabbit renal arteries by an endothelium-dependent, nitric oxide (NO)- and prostaglandin-independent mechanism. The aim was to identify the responsible P1-purinoceptor subtype and to investigate the involvement of K+-channels. METHODS: Rabbit renal arteries were perfused with medium containing indomethacin (10 micromol/l). After preconstriction with noradrenaline (0.4 micromol/l), changes in vessel diameter by P1-purinoceptor agonists were measured with a photoelectric device. The P1-receptor subtype was characterised by selective antagonists. RESULTS: Adenosine caused concentration-dependent dilation (EC50 approximately 7 micromol/l). The mRNA for A1, A2A and A3 receptors were demonstrated by reverse transcription-polymerase chain reaction from total RNA of renal arteries. The agonists CPCA (A2) and CGS21680 (A2A) dilated renal arteries (EC50 approximately 0.1 micromol/l), and CPA (A1) was ineffective. As demonstrated by experiments using two arteries in sequence, CPCA induced release of an endothelium-derived relaxing factor. NO synthase inhibition by NG-nitro-L-arginine methyl ester (L-NAME) had no effect on CPCA-induced dilation. The concentration-response curves of adenosine, CPCA and CGS21680 were shifted to the right by the A2A antagonist ZM241385 (1 micromol/l), but not by the A1 and A3 antagonists DPCPX (1 micromol/l) and MRS1220 (1 micromol/l). Iberiotoxin (0.1 micromol/l), a blocker of Ca2+-activated K+-channels, slightly shifted the dose- response curve of CPCA. Arteries preconstricted by KCl showed dilation to CPCA, but not to acetylcholine chloride (ACh). CONCLUSION: Adenosine induces dilation of rabbit renal arteries through activation of A2A receptors. This effect depends on the release of an endothelium-derived relaxing factor, which is not NO. Dilation by ACh in the presence of L-NAME is likely to be mediated by K+ as an endothelium-derived relaxing factor. However, in the A2A-receptor-induced dilation of rabbit renal arteries, K+ does not play this role, suggesting the involvement of a further soluble factor in the receptor-induced dilatory function of the endothelium.

Adenosine↗
PubMed1999

Neuropeptide Y and ATP interact to control renovascular resistance in the rat.

Neuropeptide Y (NPY) and ATP are cotransmitters of norepinephrine (NE). Modulation of ATP-mediated purinergic neurotransmission by NPY was investigated in rat perfused kidney. Beta,gamma-Methylene-L-ATP (beta,gamma-mATP; 1.0 to 1.5 microM, n = 8), NE (0.1 microM, n = 8), and NPY (0.1 microM, n = 14) increased perfusion pressure by maximally 12 +/- 1, 17 +/- 2, and 9 +/- 1 mmHg, respectively. In the presence of NPY, responses to ATP and NE were dramatically enhanced. Renal nerve stimulation in the presence of the alpha-adrenoceptor antagonist phentolamine (1 microM) induced pressor responses of 54 +/- 5 mmHg (n = 6). Alpha-blockade-resistant responses were abolished by the P2-purinoceptor blocker suramin (300 microM) and thus mediated by ATP. Purinergic responses were also reduced significantly (50%) by the NPY-Y1 receptor blocker BIBP 3226 (1 microM). NPY (0.1 microM) potentiated purinergic pressor responses and enhanced ATP release from 0.7 +/- 0.2 to 4.1 +/- 0.9 pmol (n = 4) associated with a significant increase of soluble ATPase activity. All NPY effects were prevented by BIBP 3226. Pressor responses to renal nerve stimulation delivered at short time intervals, mimicking enhanced sympathetic drive to the kidney, were not constant but showed a progressive rise, which was prevented by BIBP 3226. In this study, it is suggested that purinergic vasoconstriction in rat kidney depends on concomitantly released NPY. NPY by itself is only a weak vasoconstrictor but acts as a modulator of renal vascular resistance by enhancing the effects of its sympathetic cotransmitters, especially during sympathetic overactivity.

Adenosine Triphosphatases↗
PubMed1998

Purinoceptors mediate renal vasodilation by nitric oxide dependent and independent mechanisms.

BACKGROUND: Adenosine triphosphate (ATP) and its metabolites including adenosine modulate renal vascular tone under physiological and pathophysiological conditions. Their effects are brought about by activation of membrane bound P1- and P2-purinoceptors located on smooth muscle and endothelial cells. In this study we analyzed the purinoceptor mediated dilation of rabbit and human renal arteries, and evaluated the possible involvement of endothelium-derived relaxing factors. METHODS: Segments of rabbit and human renal arteries were incubated and perfused with medium containing indomethacin. After preconstriction, drug induced changes in the vessel diameters were measured by a photoelectric device. RESULTS: ATP (EC50 = 1 mumol/liter), added intraluminally, caused maximal vasodilation of 80 to 100% of the preconstriction response in both species. This effect was inhibited by the P1-purinoceptor antagonist 8-p-(sulphophenyl)theophylline (100 mumol/liter), suggesting that it was in part due to breakdown of ATP to adenosine. The nature of purinoceptor mediated renal vasodilation was studied further in rabbit renal arteries. Adenosine (EC50 = 1 mumol/liter) as well as the P2Y-receptor agonists ADP beta S (EC50 = 0.4 mumol/liter) and 2-MeSATP (EC50 = 0.2 mumol/liter) dilated the arteries by 80 to 100%. The effects of 2-MeSATP, which were to a much lesser extent that of ADP beta S but not that of adenosine, were attenuated by the P2Y-antagonist reactive blue 2 (3 mumol/liter). Removal of the endothelium almost abolished the vasodilation induced by adenosine and ATP. In contrast, these dilator response were only slightly attenuated by the nitric oxide synthase blockers NG-nitro-L-arginine methyl ester and NG-nitro-L-arginine (300 mumol/liter each), whereas acetylcholine and 2-MeSATP induced dilation was markedly reduced by NG-nitro-L-arginine methyl ester. CONCLUSIONS: P1-purinoceptors activated by adenosine dilate rabbit renal arteries by an endothelium-derived relaxing factor that appears to be distinct from nitric oxide. In contrast, P2Y-purinoceptor induced renal dilation is mediated by nitric oxide. ATP, the physiological activator of P2Y-purinoceptors, is rapidly broken down to adenosine in rabbit and human renal arteries. Therefore, in rabbit and human renal arteries the vasodilatory effect of exogenous ATP mainly results from P1-purinoceptor activation probably through its breakdown product, adenosine.

Adenosine↗
PubMed1987

Efficacy of O-(beta-hydroxyethyl)-rutosides at high dosage in counteracting the unwanted activity of oral contraceptives on venous function.

In a double-blind study the effect of a high dosage of O-(beta-hydroxyethyl)-rutosides (HR) was tested in women taking oral contraceptives and suffering from venous insufficiency of the lower limbs. Ten patients were treated for 28 days with HR (3 g/day) and ten with a placebo. In basal conditions and after therapy, the symptoms of venous disorders and the venous function, by means of strain gauge plethysmography, was evaluated in both groups. The results showed an increase of venous capacitance and a reduction of venous tone in the subjects treated including those without symptoms in the lower limbs. The HR treatment resulted in a significant improvement of the venous function parameters and of the symptoms in lower limbs.

Adult↗
PubMed1986

[Treatment of acute symptoms of hemorrhoid disease with high-dose oral O-(beta-hydroxyethyl)-rutosides].

The pharmacological treatment is widely used in the therapy of haemorrhoids. An efficient treatment is particularly useful in case of haemorrhoids of 2nd, 3rd and 4th degree, when phlogosis, oedema and pain are present. Forty patients were treated with either O-(beta-hydroxyethyl)-rutosides (4 g/day orally) or placebo in a double blind randomized comparative trial. The groups of treatment were homogeneous. O-(beta-hydroxyethyl)-rutosides induced a statistically significant reduction of pain and bleeding; placebo did not induce any significant improvement. Tolerability was good and similar for both treatments. It has never been necessary to stop treatment for side effects. The results obtained in this study confirm the usefulness on administering an oral treatment, and not only a local treatment, to patients with acute symptoms of haemorrhoids, both in case of intermittent treatment and in case it is used to prepare quickly the patient for surgery.

Administration, Oral↗
PubMed1986

Clinical pharmacology of tritoqualine: a comparative study against dexchlorpheniramine in allergic rhinitis.

The effect of tritoqualine on seasonal allergic rhinitis caused by grass pollen was compared to that of dexchlorpheniramine maleate (DCPM) in 21 patients randomly allocated into two parallel groups. There were rapid improvements of all symptoms considered after treatment with either tritoqualine or DCPM. A significant reduction of plasma histamine concentrations was observed during the treatment with tritoqualine whereas no modification occurred with DCPM. Finally, it was shown that tritoqualine did not modify reaction times to visual and auditive stimuli whereas DCPM induced a significant slowing-down of the reaction time to visual stimuli. From this pilot study tritoqualine appears to have the same efficacy for the treatment of seasonal allergic rhinitis as classic anti-H1 antihistamines, but without central nervous system side-effects.

Adolescent↗
PubMed1979

[Anti-edema activity of injectable Venoruton in abdominal surgery].

The anti-oedema activity of an injectable drug (HR; active principle: 0-(beta-hydroxyethyl)-rutoside) was assessed in 60 gastric extrahepatic bile duct, and large intestine surgery patients (30 being used as controls). Gastroscopy (with biopsy), gastroduodenoscopy, colonoscopy (with biopsy) and radiological examination were usually performed on the 5th and 10th post-operative days. The drug showed significant therapeutic effects: rapid resolution of oedema, especially at the sutures, leading to early cicatrisation, canalisation and the prevention of dehiscence. Finally, duration of hospitalisation was less than in the untreated cases. The gastroscopic, radiographic and biopsy findings are considered to have shown clear evidence of the drug's action against oedema formation.

Adult↗
PubMed1978

Evaluation of the local antihistaminic activity of dimetindene maleate by a quantitative method.

The topical application of a 0.1% dimetindene maleate gel on the forearms of 11 subjects reduces the areas of both erythema and wheal produced by the intradermal injection of 0.025 mg of histamine hydrochloride to a statistically greater degree than 1% d-chlorpheniramine maleate cream (p less than 0.005 and p less than 0.0005, respectively). The quantitative method employed in this study has proved to be an excellent means for the evaluation of the antihistaminic activity of topical preparations.

Administration, Topical↗