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E Noack

Publications and source records attributed to E Noack.

At least 19 recordsLinked to original sources
PubMed1996

Low increase in cGMP induced by organic nitrates and nitrovasodilators improves contractile response of rat ventricular myocytes.

Whether organic nitrates are bioactivated to NO in cardiac muscle cells and may thus directly affect cardiac contractile function has remained an open question. Therefore, we determined the effects of the organic nitrates glyceryl trinitrate (100 mumol/L), pentaerythritol tetranitrate (10 mumol/L), and isosorbide-5-mononitrate on electrically stimulated contractile response (CR) and cAMP and cGMP content of isolated adult rat ventricular cardiomyocytes compared with different concentrations of the spontaneous NO donors S-nitroso-N-acetyl-d,1-penicillamine (SNAP) and 2,2-diethyl-1-hydroxy-1-nitroso-hydrazine (DEA/NO). A high concentration of spontaneous NO donors (100 mumol/L caused a large increase in cGMP content that was accompanied by a decrease in CR to 73.8 +/- 6.7% (SNAP) and 80.9 +/- 6.1% (DEA/NO) of the control values. Inhibition of cGMP-dependent protein kinase by 10 mumol/L KT 5822 converted this effect into a pronounced improvement of CR (163.5 +/- 14.0%) By contrast, the organic nitrates caused a small but significant increase in cGMP, which was accompanied by an increase in cAMP and CR identical to that induced by 10 nmol/L isoprenaline (141.6 +/- 6.4%) A similar effect was observed with a low concentration (1 mumol/L of SNAP and DEA/NO. All increases in CR induce by nitrates were abolished after inhibition of cAMP-dependent protein kinase by Rp-cAMPS (10 mumol/L). The positive contractile effect of isoprenaline was enhanced by 1 mumol/L SNAP. This effect was also demonstrated in isolated rat papillary muscles. These results indicate that in cardiac muscle (1) organic nitrate are bioactivated to NO; (2) this results in a moderate increase in cGMP, which causes an improved CR by increasing cAMP and activating cAMP-dependent protein kinase; and (3) a large increase in cGMP, produced by high doses of NO donors, reduces CR because of the activation of CGMP-dependent protein kinase.

Animals↗
PubMed1995

The new NO donor SPM3672 increases cGMP and improves contraction in rat cardiomyocytes and isolated heart.

Recent evidence indicates that organic nitrate esters may directly affect heart muscle. In the present study we investigated the effects of the new organic nitrate ester, N-(3-nitratopivaloyl)-1-cysteineethylester (SPM3672), on isolated adult rat ventricular myocytes and on Langendorff preparations of spontaneously beating rat hearts perfused in a volume-constant manner. In cardiomyocytes SPM3672 (100 microM) induced a significant increase in the basal level of cGMP to 232 +/- 44% (n=8) indicating its metabolism to nitric oxide. This was associated with an enhanced contractile response to electrical field stimulation (to 174 +/- 9%, n=108). In isolated hearts SPM3672 elicited a slight reduction of coronary perfusion pressure (-15 +/- 8%) and a significant increase in maximal left ventricular pressure (LVPmax), dp/dtmax and dp/dtmin amounting to 18 +/- 7%, 18 +/- 6% and 21 +/- 7% (n=7), respectively. Oxygen consumption and heart rate remained constant. Thus, SPM3672 improved the contractile response of cardiomyocytes and of isolated heart. This is probably due to the metabolism of SPM3672 to nitric oxide in ventricular cardiomyocytes.

Animals↗
PubMed1995

Comparison of the vasorelaxing effect of different nitrovasodilators in conductive arterial and venous blood vessels.

We tested classically used organic nitrovasodilators such as s-nitroso-n-acetyl-D,L-penicillamine, 3-morpholino-sydnonimine, pentaerythrityl-tetranitrate, isosorbide-dinitrate, isosorbide-mononitrate, glyceryl-trinitrate on different isolated conductive arterial and venous blood vessels of the same species (rabbit). We found an up to two orders of magnitude more pronounced venoselectivety in the systemic-circulation as compared to the lung-circulation. ISMN and PETN were most venoselective nitrovasodilators, with PETN being the most potent drug in all vessels studied.

Animals↗
PubMed1995

Effects of pentaerythrityl-tetranitrate and isosorbide-5-mononitrate in experimental atherosclerosis.

This study was performed to determine whether long-term treatment with organic nitrovasodilators exhibit pharmacological effects on the development of atherosclerotic lesions and endothelial dysfunction in the cholesterol fed rabbit. The major finding of this study is that PETN, but not ISMN, decreases the extent of aortic intimal lesions and the development of endothelial dysfunction. In addition, 15 weeks of feeding a diet enriched with either PETN or ISMN did not induce a measurable extent of vascular in-vitro tolerance to the vasodilator activity of these drugs.

Animals↗
PubMed1995

In vivo effects of pentaerythrityl-tetranitrate and isosorbide-5-mononitrate on the development of atherosclerosis and endothelial dysfunction in cholesterol-fed rabbits.

We wished to determine whether long-term treatment with organic nitrovasodilators has pharmacological effects on the development of atherosclerotic lesions and endothelial dysfunction in cholesterol-fed rabbits. For 15 weeks, six groups of 9 New Zealand White rabbits received a standard diet, which contained no admixture, pentaerythrityl-tetranitrate (PETN 6 mg/kg body weight/day), or isosorbide-5-mononitrate (ISMN 2 mg/kg body weight/day). In the other three groups, the same diets were further enriched with cholesterol (0,75%). Four rings of thoracic aorta were used for tension studies; these rings and the aortas from the aortic arch to bifurcation were then fixed in formol and stained with Sudan IV to determine the area of luminal atherosclerotic lesions by a computerized laser-scanning approach. The cholesterol diet increased plasma levels of cholesterol from 69.8 +/- 10.4 to 907.1 +/- 85.5 mg/dl. A similar result was obtained in the group receiving PETN/cholesterol, but the group fed ISMN/cholesterol showed a significantly higher plasma level of cholesterol (1,165 +/- 81.4 mg/dl). Plasma levels of PETN metabolites were still detectable by gas chromatography/mass spectrometry after a 24-h in vivo washout period. The cholesterol diet induced a pronounced degree of atherosclerotic lesions in the aortic arch and the thoracic and abdominal aorta: 73.3 +/- 1.9, 46.3 +/- 2.5, and 49.6 +/- 3.6%, respectively. Additional treatment with PETN resulted in a reduction of this atherosclerotic area to 58.6 +/- 2.05% (p < 0.0001), 34.7 +/- 1.98% (p < 0.01), and 39.3 +/- 3.06% (p < 0.05). In contrast, ISMN had no significant effect on this parameter. The cholesterol diet also induced an endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine (ACh). Treatment with PETN completely inhibited the development of endothelial dysfunction, whereas ISMN had no effect. In the three groups receiving a cholesterol diet, an increased extent of aortic lesions significantly correlated with increased endothelial dysfunction measured in the same preparations. The long-term treatment with PETN did not affect the vasorelaxing potency of PETN in aortic rings, and similar results were obtained in the case of ISMN. We conclude that long-term treatment with doses of PETN, which do not promote the development of in vitro vascular nitrate tolerance, may protect against atherosclerosis and endothelial dysfunction. This novel, yet unknown pharmacodynamic quality of nitrovasodilators like PETN may contribute to their long-term efficacy in coronary artery disease but may also imply new therapeutic indications in the future.

Acetylcholine↗
PubMed1994

Nitrovasodilator-induced relaxation and tolerance development in porcine vena cordis magna: dependence on intact endothelium.

1. Isolated segments of porcine vena cordis magna exhibited a reproducible contractile activity upon application of prostaglandin F2 alpha (PGF2 alpha) or KCl, that was independent of the presence of intact endothelium. Substance P (3 nM) elicited strictly endothelium-dependent relaxations amounting to 46.1 +/- 1.4% (n = 206) of contractions induced by 10 microM PGF2 alpha. 2. S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a compound that spontaneously liberates nitric oxide, concentration-dependently relaxed PGF2 alpha-precontracted (50 microM) venous segments. Tolerance induction (incubation with 100 microM SNAP for 30 min) within the same segments resulted in a 3 fold attenuation of this effect, which was not further reduced after additional preincubation with glyceryl trinitrate (GTN). Removal of endothelium or the presence of N omega-nitro-L-arginine methylester (L-NAME) significantly improved the potency of SNAP before and after tolerance induction. 3. Concentration-dependent relaxations induced by GTN in non-tolerant veins were similar in the presence and absence of endothelium but much more reduced in tolerant endothelium-denuded (75 fold) compared to intact (20 fold) segments. In contrast, the presence of L-NAME significantly improved GTN-activity solely in non-tolerant veins, which, therefore, also resulted in a more pronounced attenuation of activity due to tolerance induction (100 fold). Preincubation of intact veins with SNAP also reduced GTN-activity but to a lesser extent (10 fold). 4. The more delayed but much longer, and compared to GTN somewhat weaker, acting new nitrovasodilator N-(3-nitrato-pivaloyl)-1-cysteineethylester (SPM 3672) was more potent in denuded than intact non-tolerant venous segments. Induction of tolerance by GTN resulted in a 2 fold-attenuation of potency. This effect was increased to 15 fold in denuded veins but solely due to enhanced potency of SPM 3672 caused by removal of endothelium.5. These data demonstrate that intact endothelium of porcine vena cordis magna attenuates the relaxant potency of nitrovasodilators but also probably participates in vascular bioactivation of GTN.We suggest that the reduced potency of nitrovasodilators is due to endogenous production of nitricoxide, which may affect the soluble guanylate cyclase/cyclic GMP-system or inhibit nitrate bioactivation pathways.

Animals↗
PubMed1993

Influence of endothelium and nitrovasodilators on free thiols and disulfides in porcine coronary smooth muscle.

It is hypothesised that the well known development of tolerance to the vasodilating action of organic nitrates is contributed by intracellular depletion of free thiols occurring during repeated treatment with these drugs. Therefore, ring segments of porcine coronary arteries with and without endothelium were treated for 30 min with either vehicle or 100 microM of isosorbide-5-mononitrate, glyceryl trinitrate, S-nitroso-N-acetyl-D,L-penicillamine or N-(3-nitratopivaloyl)-1-cysteine-ethylester (SPM 3672), and the content of histochemically stained free thiols (-SH) and disulfides (S-S-) was measured densitometrically in single smooth muscle cells. In the presence of endothelium the content of -SH in smooth muscle cells of controls (n = 8) gave an extinction of 0.127 +/- 0.013 in the intima and 0.120 +/- 0.010 in the media. The corresponding values for S-S- were 0.684 +/- 0.084 and 0.535 +/- 0.120 (n = 8). Removal of endothelium reduced S-S- to 82.1 +/- 70% and increased -SH to 126.7 +/- 6.7%. Treatment with all nitrates reduced -SH in intact artery segments to a similar degree, ranging between 54.0 +/- 4.4 and 68.7 +/- 4.7% (n = 8-10). In contrast, S-S- content was less affected and reached values between 70.6 +/- 2.8 and 91.6 +/- 6.0% (n = 8-9). As evaluated by tension studies, tolerance developed for glycerol trinitrate and isosorbide-5-mononitrate but not for S-nitroso-N-acetyl-D,L-penicillamine. Induction of tolerance with glycerol trinitrate (0.1 mM) produced a significantly more pronounced attenuation in activity of isosorbide-5-mononitrate than tolerance induction with isosorbide-5-mononitrate (1 mM). In contrast, the potency of SPM 3672 was not reduced in glycerol trinitrate-tolerant arteries. We conclude that, in porcine coronary arteries, an intact endothelium modifies intracellular thiols and disulfides. In addition, nitrate tolerance is associated with, but probably not caused by, thiol depletion.

Analysis of Variance↗
PubMed1993

Nitric oxide liberating, soluble guanylate cyclase stimulating and vasorelaxing properties of the new nitrate-compound SPM 3672.

Development of tolerance as a consequence of organic nitrate therapy such as that which occurs with glyceryl trinitrate (GTN) appears to be associated with a depletion of free thiols in vascular smooth muscle. In this study, we investigated N-[3-nitratopivaloyl]-L-cysteineethylester (SPM 3672), a new compound containing a nitrate and a thiol moiety, in direct comparison with GTN. Liberation of nitric oxide (NO) from GTN and SPM 3672 measured in vitro was rather low and was markedly potentiated by addition of cysteine only in the case of GTN. Pronounced activation of a partially purified human soluble guanylate cyclase (sGC) by GTN was observed only after addition of cysteine, whereas a comparative activation by SPM 3672 occurred with and without addition of this thiol. In contrast, SPM 4946 (N(-)[3-hydroxypivaloyl]-L-cysteineethylester), a derivative of SPM 3672 lacking the nitrate-ester moiety, did not activate sGC. Activation of sGC by GTN and SPM 3672 was nearly abolished by oxyhemoglobin. Incubation of isolated porcine coronary artery rings with GTN or SPM 3672 resulted in a similar increase in vascular cyclic GMP levels. In rat aorta, GTN was a more potent vasorelaxant than SPM 3672 and produced a greater degree of tolerance. Vasorelaxation induced by GTN occurred with rapid onset and was brief, whereas SPM 3672 produced long-lasting relaxation with a more delayed onset. This kinetic pattern was confirmed in porcine coronary arteries, in which both nitrates exhibited marked relaxation, with GTN being slightly more potent than SPM 3672.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Thiol-mediated generation of nitric oxide accounts for the vasodilator action of furoxans.

Furoxans (1,2,5-oxadiazole-2-oxides) are widely used in organic chemistry as intermediate compounds for the synthesis of various heterocycles. Despite the fact that some furoxans have been found to possess remarkable biological activities, up to now no systematic study on their mode of action has been reported. The aim of the present study was to investigate the molecular mode of the vasodilator action of furoxans. Furoxans, but not the corresponding furazans, concentration-dependently increased coronary flow in an isolated working rat heart preparation. This effect was blunted upon coinfusion with methylene blue. All tested furoxans were demonstrated to increase potently the activity of soluble guanylate cyclase. Enzyme stimulation was found to be mediated by the generation of nitric oxide (NO) following chemical reaction of the furoxans with sulfhydryl groups of low molecular weight thiols and proteins. Furoxans are thus prodrugs which increase the level of cyclic GMP via formation of NO and may therefore be classified as nitrovasodilators. Along with the generation of NO, nitrite and nitrate ions and S-nitrosothiols were formed. The rates of formation of these metabolites, however, did not appear to be related to enzyme stimulation. A tentative reaction scheme that fits the obtained experimental data is proposed. Recently reported cytotoxic, mutagenic, immunosuppressive and anticancer effects of furoxans are discussed in the light of their ability to release NO upon reaction with thiols.

Animals↗
PubMed1991

Molecular mechanisms of nitrovasodilator bioactivation.

All nitrovasodilators act intracellularly by a common molecular mechanism. This is characterized by the release of nitric oxide (NO). They are, thus, prodrugs or carriers of the active principle NO, responsible for endothelial controlled vasodilation. The rate of NO-formation strongly correlates with the activation of the soluble guanylate cyclase in vitro, resulting in a stimulation of cGMP synthesis. Nitrovasodilators thus are therapeutic substitutes for endogenous EDRF/NO. The pathways of bioactivation, nevertheless, differ substantially, depending on the individual chemistry of the nitrovasodilator. Besides NO, numerous other reaction products such as nitrite and nitrate anions are formed. The guanylate cyclase is only activated if NO is liberated. In the case of organic nitrates such as GTN, NO is only formed if certain thiol compounds are present as an essential cofactor. The rate of NO-formation correlates with the number of nitrate ester groups and proceeds with a simultaneous nitrite formation (with a ratio of 1:14 in the presence of cysteine). Nitrosamines such as molsidomine do not need thiol compounds for bioactivation. They directly liberate NO from the ring-open A-forms. This process basically depends on the presence of oxygen as electron acceptor from the sydnonimine molecule. Therefore, besides NO also superoxide radicals are formed, which may react with the generated NO under formation of nitrate ions. Organic nitrites (such as amyl nitrite) require the preceding interaction with a mercapto group to form a S-nitrosothiol intermediate, from which finally NO radicals are liberated. Nitrosothiols (like S-nitroso-acetyl-penicillamine) and sodium nitroprusside spontaneously release NO. The molecules themselves do not possess a direct enzyme activating potency. In the presence of thiol compounds organic nitrites (e.g., amyl nitrite) and nitrosothiols may act as intermediary products of NO generation.

Amyl Nitrite↗
PubMed1990

Mechanisms of nitrate tolerance--influence of the metabolic activation pathways.

Nitrovasodilator drugs like nitroglycerin are broadly used for the treatment of coronary heart disease. They act by releasing nitric oxide, a gaseous substance that has substantial physiological importance for the regulation of vascular tone, and which is synthetized and released by the vascular endothelial cell layer. Nitrovasodilators thus are prodrugs for the release of nitric oxide (NO). Their pathways of bioactivation, however, are very different, depending on the individual chemical structure of the drugs. In the case of nitrate-containing vasodilators like nitroglycerin or ISDN an enzyme-catalyzed reduction or non-enzymatic interaction with thiol-containing compounds is a prerequisite for the liberation of NO. These specific pathways of chemical degradation are likely to trigger off the development of nitrate tolerance if sophisticated dosage regimens are not maintained, because drugs which directly release NO like sodium nitroprusside or amylinitrite do not show this phenomenon. Inhibition of enzymatic and nonenzymatic biotransformation due to oxidation of essential SH-containing compounds and/or to their cellular depletion may be, therefore, the reason for nitrate tolerance.

Animals↗
PubMed1989

Molecular aspects underlying the vasodilator action of molsidomine.

Using different techniques, we measured the kinetics of nitric oxide (NO) liberation from SIN-1, the metabolite of molsidomine, and some related sydnonimines like its thiomorpholinyl analog, compound C 78-0698, and compared it under identical experimental conditions with its biological action at the guanylate cyclase (GC) site, taking this target enzyme as a suitable bioassay. There was a close relationship between half-maximal activation of GC and the velocity of NO release. The thiomorpholinyl analog was slightly more active in NO liberation than SIN-1 and activated the enzyme more rapidly. The kinetics of SIN-1A and SIN-1C formation, determined by high-performance liquid chromatography, could be accurately described by a Bateman equation. Oxyhemoglobin shifted the concentration-response curve of SIN-1 at the isolated soluble GC concentration to the right, whereas methemoglobin was without any effect. The results of our chemical and biochemical studies suggest that velocity and amount of NO formation are the only rate-limiting factors of guanylate cyclase activation by sydnonimines like SIN-1. NO, therefore, exclusively is the mediator of their pharmacodynamic action. In remarkable contrast to nitrate esters like glyceryl trinitrate or isosorbide dinitrate, NO liberation is not dependent on the interaction with thiol-containing compounds like cysteine.

Animals↗
PubMed1989

On the mechanism of NO release from sydnonimines.

The vasodilator and antiaggregatory properties of sydnonimines like SIN-1 are thought to be due to their marked stimulatory action on soluble guanylate cyclase. Enzyme activation and consecutive cyclic GMP accumulation is mediated by the liberation of nitric oxide (NO) from the open-ring A forms of sydnonimines. The purpose of the present study was to investigate the mechanism of NO release from sydnonimines in direct comparison to their stimulatory effect at the target enzyme, soluble guanylate cyclase. All sydnonimines tested were found to spontaneously liberate NO, the rate of which closely correlated with the extent of enzyme activation. NO release occurred nonlinearly with time and became maximal at high sydnonimine concentration. The in vitro stability of the A forms neither correlated with the measured rate of NO release nor with enzyme activation, indicating that a direct stimulation of guanylate cyclase by the A forms is rather unlikely. Besides NO, all sydnonimines generated NO2- and NO3- at a nearly equimolar rate. The addition of cysteine induced a marked shift from NO3- to NO2- with a small reduction in NO release, which is paralleled by a weak rightward shift of the EC50 at the guanylate cyclase. All tested sydnonimines were found to consume molecular oxygen at rates that closely corresponded to the measured rates of NO formation. By a molar comparison, the amounts of consumed oxygen are clearly higher, as would be expected for the oxidative conversion of NO to NO2- and NO3-. Oxygen seems to be additionally involved in the induction of NO formation while being converted to superoxide (O2-). In accordance with an autocatalytic process, O2- further enhances sydnonimine decomposition, since in the presence of superoxide dismutase (SOD) the rate of SIN-1C and NO2-/NO3- formation from SIN-1A was reduced, whereas the rate of NO liberation seemingly increased. O2- has, however, no influence on the rate of hydrolysis of SIN-1 to SIN-1A. At the level of guanylate cyclase, the presence of SOD induced a leftward shift of the concentration-response curve to SIN-1, in agreement with an enhancement of efficacy of NO by blocking the NO-scavenging effect of O2-. An additional O2- generation markedly enhanced SIN-1A decomposition to NO2-/NO3- and reduced the apparent rate of NO formation. We conclude from our results that oxygen plays a key role in the decomposition of sydnonimines and thus in the formation of NO as their pharmacodynamically active principle. Oxygen attack most probably occurs by one-electron abstraction from the A form of the respective sydnonimine compound.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Assessment of beta-blocking activity of low-dose bupranolol.

In the present study an investigation was made on the pharmacodynamic effect of the beta-blocking agent bupranolol in the low-dose range. Bupranolol is usually given in doses of 100 mg twice daily in the treatment of hypertension, however the dose range between 20 and 100 mg was studied using graded isoproterenol injections in healthy volunteers. A significant beta-1-blocking activity was observed for the 20 mg dose already. This effect was reduced after a treatment of 10 days. The effect increased with the higher doses, there might be a linear correlation between the logarithm of the dose and the reduction of the tachycardia after the isoproterenol injections in the low-dose range. It was concluded that using the safe and sensitive isoproterenol injection method, the clinical effect of very low doses of bupranolol may be demonstrated. The low dose might be useful to reduce the reflex tachycardia seen in the treatment of hypertension with vasodilating drugs.

Adrenergic beta-Antagonists↗
PubMed1988

Quantitative and kinetic characterization of nitric oxide and EDRF released from cultured endothelial cells.

Endothelial cells (EC) contribute to the control of local vascular diameter by formation of an endothelium derived relaxant factor (EDRF) (1). Whether nitric oxide (NO) is identical with (EDRF) or might represent only one species of several EDRFs has not been decided as yet (2-5). Therefore, we have directly compared in cultured EC the kinetics of NO formation determined in a photometric assay with the vasodilatory effect of EDRF and NO in a bioassay. Basal release of NO was 16, 4 pmol/min/ml packed EC column. After stimulation with bradykinin (BK) and ATP onset of endothelial NO release and maximal response preceded the EDRF-mediated relaxation. Concentrations of NO formed by stimulated EC were quantitatively sufficient to fully explain the smooth muscle relaxation determined in the bioassay. Our data provide convincing evidence that under basal, BK and ATP-stimulated conditions 1. endothelial cells release nitric oxide as free radical, 2. nitric oxide is solely responsible for the vasodilatory properties of EDRF.

Adenosine Triphosphate↗
PubMed1988

Additive competitive interaction of verapamil and quinidine at alpha-adrenergic receptors of isolated cardiac guinea pig myocytes and human platelets.

Recent clinical work has questioned the safety of a combined therapy of oral quinidine and intravenous verapamil, because some patients were reported to react with severe hypotension probably due to drug interactions with vascular alpha-adrenergic receptors. In order to obtain further quantitative information on the underlying mechanism, we used the radioligands (3H)-prazosin and (3H)-yohimbine to perform binding studies on intact cells, with predominantly alpha-1 (isolated myocytes) or alpha-2 subtypes (human platelets) of adrenergic receptors. Our studies confirm that both verapamil and quinidine possess a distinct alpha-adrenergic receptor blocking activity and do not discriminate between the alpha-1 and alpha-2 subtype (Ki-values were between 0.24-0.28 mumol/l for alpha-1 receptors and 0.49-0.50 mumol/l for alpha-2 receptors). Their interaction was competitive and in the presence of both drugs inhibition of radioligand binding was additive. The alpha-adrenergic blockade by verapamil was stereospecific as D-verapamil increased the dissociation constant of the radioligand to a much lesser degree than L-verapamil (Ki = 1.67 +/- 0.29 mumol/l for D-verapamil). The calcium channel blocker nitrendipine, a 1,4-dihydropyridine derivative, did not show any competition up to concentrations of 10 mumol/l. Our results thus give evidence that verapamil and quinidine have already at therapeutic blood levels significant alpha-adrenergic blocking activities which may be of clinical interest. In addition our results show that adult cardiac myocytes are very well suited for pharmacological adrenergic interaction studies.

Animals↗