Renate Rösen

• University of Cologne

It became evident in the last years that an increased vascular risk is not only associated with frank diabetes, but also already with states of insulin resistance. This risk does not only affect the large vessels contributing to the augmented cardiovascular risk often observed in insulin resistant patients, but also various functions of the microva...

The vascular NAD(P)H oxidase contributes to endothelial dysfunction and high blood pressure in the spontaneously hypertensive rat by enhancing superoxide production. We investigated the effects of apocynin, a NAD(P)H oxidase inhibitor, on blood pressure and vascular radical and nitric oxide formation in SHR and compared its effects to the calcium c...

Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies. Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure (BP) due to the action of the cocoa polyphenols, but the clinical effect of low habitual cocoa intake...

Epidemiological evidence suggests blood pressure-lowering effects of cocoa and tea. We undertook a meta-analysis of randomized controlled trials to determine changes in systolic and diastolic blood pressure due to the intake of cocoa products or black and green tea. MEDLINE, EMBASE, SCOPUS, Science Citation Index, and the Cochrane Controlled Trials...

Dihydropyridines and angiotensin converting enzyme inhibitor effects on superoxide and nitric oxide (NO) were compared in high glucose (20 mM, 24 h)-treated human Ea.hy 926 endothelial cells. High glucose stimulated superoxide both extracellularly (lucigenin chemiluminescence, cytochrome c reduction) and intracellularly (dihydrorhodamine 123 fluore...

The effects of dihydropyridine Ca2+ channel blockers (DHP) and ACE inhibitors on superoxide formation and nitric oxide (NO) bioavailability were compared in human EA.Hy926 endothelial cells (EC). EC were stimulated 4 h with angiotensin II (Ang II, 10 nM) +/- study drugs. Specific superoxide formation was measured by lucigenin-enhanced chemiluminesc...

There is evidence that dihydropyridine calcium antagonists (DHP) play a beneficial role during the development of atherosclerosis. Since antioxidative properties of this substance class may be important, we investigated the antioxidative potency of the DHP prototype calcium channel antagonist nifedipine, the long acting calcium channel antagonist l...

Chronic exposure to high concentrations of glucose has consistently been demonstrated to impair endothelium-dependent, nitric oxide (NO)-mediated vasodilation. In contrast, several clinical investigations have reported that acute exposure to high glucose, alone or in combination with insulin, triggers vasodilation. The aim of this study was to exam...

A simple and sensitive method is presented to measure the unstable molecule nitric oxide (NO) by reconversion of nitrate/nitrite to NO. Nitrate and nitrite are the stable degradation products of NO that accumulate in supernatants of biological samples that release nitric oxide. First, nitrate is enzymatically converted to nitrite using nitrate redu...

Plant phenols may exert protective effects by scavenging superoxide, which is implicated in tissue damage and accelerated inactivation of vasorelaxing nitric oxide. Preventing the interaction of superoxide with tissue biomolecules depends not only on the extent of superoxide scavenging but also on scavenging velocity. However, information on supero...

Several experimental and clinical studies have demonstrated the antiatherogenic profile of the long-acting calcium antagonist amlodipine. Given the pivotal role of endothelial (dys)function during atherogenesis, we investigated the influence of amlodipine on endothelial nitric oxide (NO) bioavailability. Acute addition of amlodipine to segments of...

Dihydropyridine calcium antagonists play an important role in the treatment of hypertension and angina pectoris. They lower blood pressure by a well-characterized mechanism of blocking L-type calcium channels in smooth muscle cells. Additionally, there is growing evidence that dihydropyridines also modulate endothelial functions by other mechanisms...

Dihydropyridine calcium antagonists play an important role in the treatment of hypertension and angina pectoris. They lower blood pressure by a well-characterized mechanism of blocking L-type calcium channels in smooth muscle cells. Additionally, there is growing evidence that dihydropyridines also modulate endothelial functions by other mechanisms...

The aim of this study was to investigate whether the HMG-CoA reductase inhibitor cerivastatin alters the nitric oxide (NO) bioavailability of porcine aortic endothelial cell cultures and of native porcine coronary endothelium, after short-term (minutes) and long-term (24-hour) treatment with cerivastatin (electrochemical NO sensor). NO-synthase exp...

The high intake of polyphenols is thought to contribute to the beneficial cardiovascular effects of plant-centered diets. A putative mechanism underlying the cardioprotective activity is thought to be a plant phenol-induced increase of nitric oxide formation by the constitutive endothelial nitric oxide synthase. Twenty-eight phenols of different cl...

It has not been completely clarified whether selective estrogen receptor modulators (SERMs) such as raloxifene exert vasoprotective effects similar to those of estrogens. To investigate vascular effects of raloxifene, male spontaneously hypertensive rats were treated for 10 weeks with either raloxifene (10 mg x kg(-1) x d(-1)) or vehicle. Raloxifen...

Studien zur Rolle von Superoxidanion-Radikalen bei der Kardiotoxizität von Adrenochrom Adrenochrom ist ein Oxidationsprodukt von Adrenalin und besitzt kardiotoxische Eigenschaften. Da die kardiotoxischen Wirkungen von Katecholaminen z. T. durch freie Sauerstoffradikale vermittelt werden, wurde die Rolle von Superoxidanion-Radikalen als Vermittler f...

Different observations suggest that dihydropyridine calcium antagonists alter endothelial NO release. Therefore, in a first step we investigated whether part of the nisoldipine (a dihydropyridine calcium antagonist with a possible selectivity for coronaries)-induced vasorelaxation was due to an NO release from the endothelium in porcine coronary ar...

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) significantly reduce cardiovascular mortality associated with hypercholesterolemia. There is evidence that statins exert beneficial effects in part through direct effects on vascular cells independent of lowering plasma cholesterol. We characterized the effect of a 30-da...

Short-term treatment of the endothelium with dihydropyridine calcium antagonists resulted in an increased release in NO that is not due to a modulation of L-type calcium channels, because macrovascular endothelial cells do not express this channel. We investigated whether long-term (48 hours) treatment of porcine endothelial cell cultures with the...

Postmenopausal estrogen deficiency is associated with an increased cardiovascular risk, hypertension, and oxidative stress. Angiotensin type 1 (AT(1)) receptor regulation is involved in the pathogenesis of atherosclerosis. To characterize vascular function, oxidative stress, and AT(1) receptor regulation during estrogen deficiency, ovariectomized s...

There are different methods to measure the unstable molecule nitric oxide (NO). We will describe a new sensitive method to measure NO by reconversion of nitrate/nitrite to NO, which will be determined with an amperometric Clark-type electrode. Nitrate and nitrite are the degradation products of NO. First, nitrate is enzymatically converted to nitri...

Different methods to measure the unstable radical nitric oxide (NO) have been established. We are going to present a new method to measure intracellular calcium and NO simultaneously in endothelial cells. A new fluorescent dye (DAF-2) has been developed recently which binds NO resulting in an enhanced fluorescence. We loaded porcine aortic endothel...

This study was undertaken to investigate the influence of exogenous NO on intracellular calcium levels of porcine aortic endothelial cell culture monolayers. Spontaneous NO liberating substances with different half-life periods (NOC-9 [10 micromol/L] approximately 1 min, SNAP [10 micromol/L] approximately 4 h), and an aqueous NO gas solution [130 n...

Background: The dihydropyridine-induced vasorelaxation is partly dependent on the endothelium, which does not express L-type calcium channels. Because nitric oxide (NO) is one of the most important endothelium-derived vasorelaxing factors, we investigated how the calcium antagonist nifedipine and the calcium agonist Bay K 8644 modulate intracellu l...

BACKGROUND: The dihydropyridine-induced vasorelaxation is partly dependent on the endothelium, which does not express L-type calcium channels. Because nitric oxide (NO) is one of the most important endothelium-derived vasorelaxing factors, we investigated how the calcium antagonist nifedipine and the calcium agonist Bay K 8644 modulate intracellula...

In recent years it has become clear that insulin resistance is both a typical characteristic of non-insulin-dependent (type 2) diabetes (NIDDM) and a common feature, and presumably the pathophysiological cause, of the 'metabolic syndrome' ('insulin resistance syndrome' or 'syndrome X') which describes the close association between various cardiovas...

The vasorelaxation caused by dihydropyridine calcium antagonists is in part dependent on the endothelium and platelet activation/aggregation is inhibited by dihydropyridines. Both cell types are lacking L-type calcium channels, the typical target of nifedipine, therefore this calcium antagonist must act via a completely different mechanism. Since b...

We tried to characterize the porcine platelet nitric oxide (NO) synthase and its L-arginine (L-arg)/NO metabolism. Using RT-PCR we could show a constitutive endothelial NOS (ecNOS) and an inducible NOS (iNOS) similar mRNA in platelets. The NOS protein could be evidenced by an ecNOS specific antibody which also bound in platelets. This finding could...

We examined the influence of the new angiotensin-converting enzyme inhibitor (ACEI) fosinopril on function and perfusion of the diabetic rat heart. Streptozotocin-diabetic rats (60 mg/kg body weight) were treated with fosinopril (10 mg/kg body weight/day) for 4 months. Cardiac performance was analyzed in the isolated heart perfused at constant volu...

1. The antiischemic properties of the flavonoids acetylvitexin-rhamnoside (AVR) and luteolin-7-glucoside-(LUT), combining phosphodiesterase (PDE)-inhibitory and antioxidant properties, were studied in comparison to amrinone (AMR) or superoxide dismutase (SOD). The effects of the new dihydropyridine-type calcium-agonist Bay T 5006 were studied in co...

The aim of this study was to examine the influence of inhibition on angiotensin converting enzyme (ACE) of myocardial function and perfusion of the rat impaired by diabetes. Spontaneously diabetic rats were treated with the ACE-inhibitor captopril for 4 months. Cardiac performance was analysed in the isolated heart perfused at constant volume. Epic...

1. The functional effects of the flavonoid luteolin-7-glucoside (LUT) were investigated in Langendorff-rabbit hearts perfused at constant pressure. Repetitive myocardial ischemia was induced by coronary artery ligature and quantified from NADH-fluorescence photography. 2. LUT significantly enhanced left ventricular pressure and the global and relat...

The in vitro effect of nifedipine, a calcium channel blocker of the dihydropyridine (DHP) type, on platelet aggregation was reinvestigated considering especially the capability of platelets to form endogenous nitric oxide (NO). We studied the dose-dependent antiaggregatory property of nifedipine in porcine platelet rich plasma. Aggregation was stim...

Unlabelled: Several phosphodiesterase inhibitors have been reported to possess antiischaemic properties by improving myocardial oxygen demand/supply balance. Levosimendan is a new phosphodiesterase inhibitor with calcium-sensitizing properties. We investigated the functional and antiischaemic properties of levosimendan in isolated electrically-dri...

1. Human platelet aggregation induced by collagen is concentration-dependently inhibited by dihydropyridine (DHP)-type calcium(Ca)-agonists. 2. There was no significant difference between the maximal anti-aggregatory effects or the anti-aggregatory potencies of (-)-S-Bay-K 8644 (EC50: 5.3 +/- 1.5 x 10(-5) M), (+/-)-Bay-W 5035 (EC50: 14.9 +/- 8.8 x...

The effect of inotropes on myocardial ischemia is difficult to predict because they may influence the determinants of myocardial O2 demand and O2 supply differently. Several PDE-inhibitors have been reported to possess antiischemic properties related to their hemodynamic and O2-sparing effects. To assess whether PDE-inhibitors also possess direct c...

The anti-ischemic properties of the ACE inhibitor ramiprilat (ram) were investigated in electrically driven Langendorff hearts from rabbits whose endogenous angiotensin-I content has been previously shown to be very low (constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l). Cumulative concentration-response curves showed that the reducti...

Unlabelled: Several beta-adrenoceptor-blocking agents have been shown to possess free radical scavenging properties. Therefore, the direct cardioprotective properties of propranolol or pindolol were investigated in comparison to superoxide dismutase (SOD). We used isolated rabbit hearts paced at a constant rate (Langendorff, constant pressure: 70...

Calcium (Ca) agonists like Bay k 8644 ((-)-S-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate (CAS 93468-89-4), may represent a new principle in the treatment of heart failure. Because of marked vasoconstrictive properties, these agents may have a deleterious effect on myocardial ischemia (MI). It was however demo...

Catecholamines play a major role during initiation and propagation of myocardial ischemia (MI). Therefore their influence on the size of an acute regional MI was investigated in isolated, coronary ligated rabbit hearts during electrical pacing at different rates (Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l). MI was q...

Oxygen-derived free radicals may contribute to tissue injury in myocardial ischemia although the mechanism is unclear. Catecholamines possibly could be involved in the genesis of free radicals because it has been demonstrated that oxygen free radicals may be generated by autooxidation of noradrenaline. Superoxide dismutase (SOD) protects the myocar...

The endogenous activity of the local renin-angiotensin system (RAS) and the anti-ischaemic properties of captopril were investigated in electrically driven rabbit Langendorff hearts (constant pressure: 70 cmH2O, Tyrode solution, Ca2+ 1.8 mmol.l-1). Cumulative concentration-response curves showed no significant difference (P > 0.05) between the redu...

Recent studies suggest endothelium to be involved in the vasorelaxation of calcium antagonists of the 1,4-dihydropyridine type, which may at least in part be mediated by endothelium-derived relaxing factor (EDRF = NO). To study this effect further, the influence of L-NG-nitro arginine (L-NNA), a specific inhibitor of EDRF-synthesis, on nitrendipine...

For further examination of the interaction of platelets with coronary endothelium in more detail, porcine platelets were infused into the coronary system of isolated, Langendorff-perfused rabbit hearts. The hearts were preincubated with very low activity of collagenase inducing functional endothelial lesion characterized by 50% reduction of EDRF-de...

The objective of this study was to determine the effect of nimodipine on infarct development and local brain pH after middle cerebral artery occlusion in the rat. Female Fischer-344 rats were subjected to permanent occlusion of the left middle cerebral artery by electrocoagulation. After 6, 12, or 24 hours, brains were frozen, and infarct size, deg...

In isolated Langendorff-perfused rabbit hearts concentration-response relations for histamine were analysed with and without H2-receptor blocker cimetidine (10(-5) mol l-1). The diameter of large epicardial coronary arteries was determined by video angiometry. Global coronary flow and left ventricular isovolumetric pressure were continuously regist...

Glyceryl trinitrate (GTN) induced relaxation was investigated in preparations of corresponding femoral arteries and veins from rabbits containing the intact endothelium in comparison to denuded vessels. Either vascular rings (app. 5 mm segments) or helical cut strips were isotonically mounted in organbaths (37 degrees C, Krebs-Henseleit-buffer). Ve...

The aim of this study was to evaluate whether there are vascular alterations in diabetes prior to atherosclerotic lesions. Four and 12 weeks after induction of diabetes (streptozotocin, 60 mg/kg b.w.) in rats characterized by low plasma insulin, hyperglycaemia, glucosuria, and loss of body weight, however, without morphological alterations of the c...

In isolated coronary ligated rabbit hearts the effects of washed human platelets on the size of the epicardial ischaemic area and on recovery from ischaemia during 60 min of reperfusion was evaluated by endogenous NADH-surface-fluorescence photography. Infusion of washed human platelets to non-ischaemic control hearts produced a decrease in left ve...

Glyceryltrinitrate (GTN)-induced relaxation was examined in helical strips of rabbit femoral and mesenteric vessels after precontraction with norepinephrine (EC-50). Concentration-response curves over a wide concentration range (10(-9) to 3 X 10(-4) mol/l) appeared to be biphasic with a plateau at 10(-6) mol/l. Threshold concentrations for relaxati...

In isolated coronary-ligated rabbit hearts, quantification of epicardial flow distribution pattern and of ischemic area was performed from flow indicator and endogenous NADH-fluorescence pictures, respectively, after UV-flash photography. After being digitized (256 X 256 pixels), the fluorescence photos were analyzed by an Apple desk computer using...

In perfused hearts of streptozotocin-diabetic rats the kinetics of a fluoresce indicator transit was measured after pulse injection of FITC-dextran 3. The fluorescence changes on the left ventricle could be described by two pseudo first-order processes with half times in the range of seconds (t/2) corresponding to the intravascular washout and a sl...

In Langendorff-perfused guinea pig hearts, local myocardial perfusion was evaluated by analysis of FITC-dextran-150 elution kinetics after bolus injection. Locally estimated half-times of the monoexponential elution curves showed good correlation with global undisturbed coronary flow. After ligation of the left anterior descending coronary artery i...

The effect of prostacyclin (PGI2, 0.5 nmol . kg-1 . min-1,i.v.) on myocardial metabolism was studied in cats subjected to 5 h of myocardial ischemia (MI) and compared to vehicle-treated MI cats. MI was followed by a 52% decrease in ATP and a concomitant increase (2-3 fold) in lactate and lactate/pyruvate ratio in the severely ischemic area. PGI2 pr...

In isolated guinea pig hearts epicardial perfusion was estimated by analysis of the transit profile of different fluorescence indicators. Several coronary dilating agents were tested with regard to their influence on local perfusion kinetics revealing distinct patterns of microcirculatory drug action.

The action of the non-steroidal antiinflammatory drugs indomethacin, tiaprofenic acid, diclofenac and meclofenamate on vascular and plateletcyclooxygenases was studied by measuring the arachidonic acid-induced thromboxane A2 (TXA2)-formation of washed human platelets and prostacyclin (PGI2)-formation of bovine coronary artery rings. TXA2 was bioass...

The action of prostacyclin (PGI2) on several biochemical and physiological parameters of myocardial function and coronary perfusion was studied in the rat heart in vitro, perfused according to Langendorff either at constant pressure (65 mmm Hg) or at constant volume (8 ml/min). PGI2 dose-dependently decreased coronary vascular resistance, the ED50,...

Local myocardial perfusion was studied on isolated guinea pig hearts using the fluorescence indicator technique. Wash in and wash out kinetics of fluoresceinisothiocarbamyl-dextran 3000 (FITC-dextran 3) as well as steady state fluorescence were continuously measured at the left ventricular surface using a microscope fluorimeter and correlated to th...

Rigid lipid areas (boundary lipid) form haloes around the cytochrome P–450 system.

The binding of digitoxigenin to lecithin model membranes was investigated by application of electron spin- and nuclear magnetic resonance methods. A digitoxigenin spin-label derivative was found to bind specifically to the pseudohexagonal rigid lattice of lecithin membranes. The binding is accomplished by some of the structural features which are r...

D IETS RICH IN FRUITS AND VEG-etables are among the rec-ommended lifestyle modifi-cations to lower blood pressure (BP) and to reduce cardiovas-cular disease risk, specifically in pre-hypertension or stage 1 hyperten-sion. 1,2 Although a variety of factors may contribute to the beneficial effects of plant foods, much attention has been given to the...

Hannover, Techn. Univ., Fak. f. Mathematik u. Naturwiss., Diss. 1974.