bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of cyclic nucleotides in vasodilations of the rat thoracic aorta induced by adenosine analogues
Authors: Hourani Susanna M O , Boon Katherine , Fooks Helen M , Prentice Deborah J 
Published: January 2005

Although adenosine analogues such as 5′‐N‐ethylcarboxamidoadenosine (NECA) relax the rat thoracic aorta in a partially endothelium‐dependent manner via adenosine A2A receptors, others such as N6‐R‐phenylisopropyladenosine (R‐PIA) act via an endothelium‐independent, antagonist‐insensitive mechanism. The role of cyclic nucleotides in these relaxations was investigated in isolated aortic rings using inhibitors of adenylate and guanylate cyclases as well as subtype‐selective phosphodiesterase inhibitors.
The adenylate cyclase inhibitor 9‐(tetrahydro‐2‐furanyl)‐9H‐purin‐6‐amine (SQ 22536; 100 μM) significantly inhibited responses to NECA, but not responses to R‐PIA. The type IV (cyclic AMP‐selective) phosphodiesterase inhibitor 4‐[(3‐butoxy‐4‐methoxyphenyl)methyl]‐2‐imidazolidinone (RO 20‐1724; 30 μM) significantly enhanced responses to NECA and to a lesser extent those to R‐PIA.
The guanylate cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3a]quinoxalin‐1‐one (ODQ; 100 μM) significantly inhibited responses to NECA and acetylcholine but not responses to R‐PIA. The selective phosphodiesterase V (cyclic GMP‐selective) inhibitors, zaprinast (10 μM) and 4‐{[3′,4′‐(methylenedioxy)benzyl]amino}‐6‐methoxyquinazoline (MMQ; 1 μM), had no significant effect on responses to either NECA or R‐PIA, but enhanced responses to acetylcholine.
These results are consistent with the effects of NECA being via activation of endothelial receptors to release NO which stimulates guanylate cyclase, as well as smooth muscle receptors coupled to stimulation of adenylate cyclase. The lack of effect of zaprinast and MMQ on responses to NECA are likely to be due to simultaneous activation of both adenylate and guanylate cyclases in the smooth muscle, as cyclic AMP reduces the sensitivity of phosphodiesterase V to inhibitors. These results also suggest that the effects of R‐PIA are via neither of these mechanisms.

British Journal of Pharmacology (2001) 133, 833–840; doi:10.1038/sj.bjp.0704140
Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat small resistance arteries
Authors: Côrtes Steyner F , Rezende Bruno A , Corriu Catherine , Medeiros Isac A , Teixeira Mauro M , Lopes Miguel José , Lemos Virgínia S 
Published: January 2005

The hypotensive and vasorelaxant effect of dioclein in resistance mesenteric arteries was studied in intact animals and isolated vessels, respectively.
In intact animals, initial bolus administration of dioclein (2.5 mg kg−1) produced transient hypotension accompanied by an increase in heart rate. Subsequent doses of dioclein (5 and 10 mg kg−1) produced hypotensive responses with no significant change in heart rate. NG‐nitro‐L‐arginine methyl ester (L‐NAME) did not affect the hypotensive response.
In endothelium‐containing or ‐denuded vessels pre‐contracted with phenylephrine, dioclein (5 and 10 mg kg−1 produced a concentration‐dependent vasorelaxation (IC50=0.3±0.06 and 1.6±0.6 μM, respectively) which was not changed by 10 μM indomethacin. L‐NAME (300 μM) produced a shift to the right.
Dioclein was without effect on contraction of vessels induced by physiological salt solution (PSS) containing 50 mM KCl and the concentration dependence of dioclein's effect on phenylephrine induced contraction was shifted to the right in vessels bathed in PSS containing 25 mM KCl.
Tetraethylammonium (10 mM) and BaCl2 (1 mM) increased the IC50 for dioclein‐induced vasorelaxation without affecting the maximal response (Emax). Charybdotoxin (100 nM), 4‐aminopyridine (1 mM) and iberiotoxin (100 nM) increased the IC50 and reduced the Emax. Apamin (1 μM) reduced the Emax without affecting the IC50.
Dioclein produced a hyperpolarization in smooth muscle of mesenteric arteries with or without endothelium (7.7±1.4 mV and 12.3±3.6 mV, respectively).
In conclusion dioclein lowered arterial pressure probably through a decrease in peripheral vascular resistance. The underling mechanism implicated in the vasorelaxant effect of dioclein appears to be the opening of KCa and Kv channels and subsequent membrane hyperpolarization.

British Journal of Pharmacology (2001) 133, 849–858; doi:10.1038/sj.bjp.0704147
Molecular cloning, pharmacological properties and tissue distribution of the porcine 5‐HT1B receptor
Authors: Bhalla Pankaj , Sharma Hari S , Ma Xiaoqian , Wurch Thierry , Pauwels Petrus J , Saxena Pramod R 
Published: January 2005

Using a combination of RT – PCR and inverse‐PCR techniques, we amplified, cloned and sequenced a full‐length porcine 5‐HT1B receptor cDNA derived from porcine cerebral cortex. Sequence analysis revealed 1170 bp encoding an open reading frame of 390 amino acids showing a 95% similarity with the human 5‐HT1B receptor.
The recombinant porcine 5‐HT1B cDNA was expressed in monkey Cos‐7 cells and its pharmacological profile was determined by radioligand binding assay using [3H]‐GR125743. The affinities of several agonists (L694247>ergotamine 5‐carboxamidotryptamine=dihydroergotamine=5‐HT>CP122638=zolmitriptan>sumatriptan) and putative antagonists (GR127935>methiothepin>SB224289>>ritanserin>ketanserin BRL15572) correlated highly with those described for the recombinant human 5‐HT1B receptor.
In membranes obtained from cells co‐expressing the porcine 5‐HT1B receptor and a mutant GαoCys351Ile protein, 5‐HT and zolmitriptan increased, while the 5‐HT1B receptor antagonist SB224289 decreased basal [35S]‐GTPγS binding, thus showing inverse agonism. The potency of zolmitriptan in the [35S]‐GTPγS binding assay (pEC50: 7.64±0.04) agreed with its affinity in displacing the antagonist [3H]‐GR125743 (pKi: 7.36±0.07).
The 5‐HT1B receptor mRNA was observed by RT‐PCR in several blood vessels, cerebral cortex, cerebellum and trigeminal ganglion. In situ hybridization performed in frontal cerebral cortex sections revealed the expression of 5‐HT1B receptor mRNA in pyramidal cells.
In conclusion, we have cloned and established the amino acid sequence, ligand binding profile and location of the porcine 5‐HT1B receptor. This information may be useful in exploring the role of 5‐HT1B receptor in pathophysiological processes relevant for novel drug discovery in diseases such as migraine.

British Journal of Pharmacology (2001) 133, 891–901; doi:10.1038/sj.bjp.0704150
Angiogenesis gene therapy to rescue ischaemic tissues: achievements and future directions
Authors: Emanueli Costanza , Madeddu Paolo 
Published: January 2005

Ischaemic diseases are characterized by an impaired supply of blood resulting from narrowed or blocked arteries that starve tissues of needed nutrients and oxygen. Coronary‐atherosclerosis induced myocardial infarction is one of the leading causes of mortality in developed countries. Ischaemic disease also affects the lower extremities. Considerable advances in both surgical bypassing and percutaneous revascularization techniques have been reached. However, many patients cannot benefit from these therapies because of the extension of arterial occlusion and/or microcirculation impairment. Consequently, the need for alternative therapeutic strategies is compelling. An innovative approach consists of stimulating collateral vessel growth, a natural host defence response that intervenes upon occurrence of critical reduction in tissue perfusion (Isner & Asahara, 1999). This review will debate the relevance of therapeutic angiogenesis for promotion of tissue repair. The following issues will receive attention: (a) vascular growth patterns, (b) delivery systems for angiogenesis gene transfer, (c) achievements of therapeutic angiogenesis in myocardial and peripheral ischaemia, and (d) future directions to improve effectiveness and safety of vascular gene therapy.British Journal of Pharmacology (2001) 133, 951–958; doi:10.1038/sj.bjp.0704155
Absence of ligand‐induced regulation of kinin receptor expression in the rabbit
Authors: Sabourin Thierry , Guay Katline , Houle Steeve , Bouthillier Johanne , Bachvarov Dimcho R , Adam Albert , Marceau François 
Published: January 2005

The induction of B1 receptors (B1Rs) and desensitization or down‐regulation of B2 receptors (B2Rs) as a consequence of the production of endogenous kinins has been termed the autoregulation hypothesis. The latter was investigated using two models based on the rabbit: kinin stimulation of cultured vascular smooth muscle cells (SMCs) and in vivo contact system activation (dextran sulphate intravenous injection, 2 mg kg−1, 5 h).
Rabbit aortic SMCs express a baseline population of B1Rs that was up‐regulated upon interleukin‐1β treatment ([3H]‐Lys‐des‐Arg9‐BK binding or mRNA concentration evaluated by RT–PCR; 4 or 3 h, respectively). Treatment with B1R or B2R agonists failed to alter B1R expression under the same conditions.
Despite consuming endogenous kininogen (assessed using the kinetics of immunoreactive kinin formation in the plasma exposed to glass beads ex vivo) and producing hypotension mediated by B2Rs in anaesthetized rabbits, dextran sulphate treatment failed to induce B1Rs in conscious animals (RT–PCR in several organs, aortic contractility). By contrast, lipopolysaccharide (LPS, 50 μg kg−1, 5 h) was an effective B1R inducer (kidney, duodenum, aorta) but did not reduce kininogen reserve.
We tested the alternate hypothesis that endogenous kinin participate in LPS induction of B1Rs. Kinin receptor antagonists (icatibant combined to B‐9858, 50 μg kg−1 of each) failed to prevent or reduce the effect of LPS on B1R expression. Dextran sulphate or LPS treatments did not persistently down‐regulate vascular B2Rs (jugular vein contractility assessed ex vivo).
The kinin receptor autoregulation hypothesis is not applicable to primary cell cultures derived from a tissue known to express B1Rs in a regulated manner (aorta). The activation of the endogenous kallikrein‐kinin system is ineffective to induce B1Rs in vivo in an experimental time frame sufficient for B1R induction by LPS.

British Journal of Pharmacology (2001) 133, 1154–1162; doi:10.1038/sj.bjp.0704158
Vasorelaxant effect of nitric oxide releasing steroidal and nonsteroidal anti‐inflammatory drugs
Authors: Keeble J , Al‐Swayeh O A , Moore P K 
Published: January 2005

The effect of several nitric oxide releasing‐non‐steroidal anti‐inflammatory drugs (NO‐NSAID) and nitroprednisolone on blood vessel relaxation in vitro and in vivo was studied. Nitroflurbiprofen (NOF; EC50, 688.8±93.8 μM), nitroaspirin (NOA; EC50, 57.9±6.5 μM), nitroparacetamol (NOPARA; EC50, 71.5±14.6 μM) and nitroprednisolone (EC50, 15.1±1.4 μM) caused concentration‐related relaxation of noradrenaline (NA)‐contracted rat aortic rings. All NO releasing compounds tested were approximately three orders of magnitude less potent than sodium nitroprusside (SNP, EC50, 35.7±3.5 nM).
The vasorelaxant effect of NOF and NOPARA in the rat aorta was potentiated by zaprinast (5 μM) and reduced by ODQ (5 μM). Flurbiprofen and paracetamol (100 μM) caused minimal (<10%) relaxation of the rat aorta and did not affect the response to SNP. The effect of NOF was unchanged in the presence of L‐NAME (100 μM; EC30, 181.8±35.1 μM cf. EC30, 125.1±17.0 μM, P>0.05) but increased by removal of the endothelium (EC30, 164.3±26.3 μM cf. EC50, 688.8±93.8 μM, P<0.05).
NOF (0.1–50 μM) produced a small but not concentration‐related vasodilation of the NA‐preconstricted (i.e. ‘high tone’) perfused rat mesentery preparation (cf. SNP, EC30, 4.4±0.7 μM). In contrast, NOF (1–100 μM) produced concentration‐related vasodilation of the ‘high tone’ perfused rat kidney with an EC50 of 33.1±4.4 μM.
Neither NOF (74 mg kg−1, i.p.) nor NOA (91.9 mg kg−1, i.p.) nor equimolar doses of flurbiprofen (50 mg kg−1, i.p.) or aspirin (50 mg kg−1, i.p.) affected mean arterial blood pressure (MAP) or heart rate (HR) of pentobarbitone‐anaesthetized rats over a 1 h period.
NO‐NSAID relax blood vessels in vitro by an NO‐dependent mechanism. The absolute vasorelaxant effect of NO releasing drug varies greatly with the choice of compound and between blood vessel preparations.

British Journal of Pharmacology (2001) 133, 1023–1028; doi:10.1038/sj.bjp.0704161
A comparison of effects measured with isotonic and isometric recording: I. Concentration‐effect curves for agonists
Authors: Barlow R B , Bond Susan M , Grant Claire , McQueen D S , Yaqoob Zeenat 
Published: January 2005

Concentration‐effect curves were obtained with carbachol tested on isolated preparations of guinea‐pig ileum taken from adjacent sites in the same animal, one recorded isotonically, the other isometrically: similar experiments were made with histamine as agonist and with carbachol on rat uterus (in oestrus).
The position and steepness of the curves was expressed as the values of [EC50] and the exponent, P: with carbachol or histamine on guinea‐pig ileum the curves were significantly steeper with isotonic recording (P<0.02, sign test) and displaced towards lower concentrations (P<0.005) but there were significant correlations (P<0.05) between values obtained with tissues from the same animal.
The curves for carbachol on the rat uterus were very steep: with isotonic recording the exponent (often eight or more) was consistently higher than with isometric (P<0.001): there was no significant displacement but there was a significant correlation (P<0.05) between values of [EC50] obtained with tissues from the same animal.
Although the results obtained by the two methods are different, they are correlated.
These effects are to be expected because with isotonic recording there can be no change in length until the tension exceeds the load and the tissue bulk sets an upper limit to shortening: the range within which an effect can be measured (the ‘operational window’) is smaller. The observed effects on [EC50] and P have been reproduced with theoretical data.

British Journal of Pharmacology (2001) 133, 1081–1086; doi:10.1038/sj.bjp.0704168
Functional characterization of coronary vascular adenosine receptors in the mouse
Authors: Flood Amanda , Headrick John P 
Published: January 2005

Coronary responses to adenosine agonists were assessed in perfused mouse and rat hearts. The roles of nitric oxide (NO) and ATP‐dependent K+ channels (KATP) were studied in the mouse.
Resting coronary resistance was lower in mouse vs rat, as was minimal resistance (2.2±0.1 vs 3.8±0.2 mmHg ml−1 min−1 g−1). Peak hyperaemic flow after 20–60 s occlusion was greater in mouse.
Adenosine agonists induced coronary dilation in mouse, with pEC50s of 9.4±0.1 for 2‐[p‐(2‐carboxyethyl)phenethylamino]‐5′‐N‐ethyl carboxamidoadenosine (CGS21680, A2A‐selective agonist), 9.3±0.1 for 5′‐N‐ethylcarboxamidoadenosine (NECA, A1/A2 agonist), 8.4±0.1 for 2‐chloroadenosine (A1/A2 agonist), 7.7±0.1 for N6‐(R)‐(phenylisopropyl)adenosine (R‐PIA, A1/A2B selective), and 6.8±0.2 for adenosine. The potency order (CGS21680=NECA>2‐chloroadenosine>R‐PIA>adenosine) supports A2A adenosine receptor‐mediated dilation in mouse coronary vessels. 0.2–2 μM of the A2B‐selective antagonist alloxazine failed to alter CGS21680 or 2‐chloroadenosine responses.
pEC50s in rat were 6.7±0.2 for CGS21680, 7.3±0.1 for NECA, 7.6±0.1 for 2‐chloroadenosine, 7.2±0.1 for R‐PIA, and 6.2±0.1 for adenosine (2‐chloroadenosine>NECA=R‐PIA>CGS21680> adenosine), supporting an A2B adenosine receptor response.
NO‐synthase antagonism with 50 μM NG‐nitro L‐arginine (L‐NOARG) increased resistance by ∼25%, and inhibited responses to CGS21680 (pEC50=9.0±0.1), 2‐chloroadenosine (pEC50=7.3±0.2) and endothelial‐dependent ADP, but not sodium nitroprusside (SNP). KATP channel blockade with 5 μM glibenclamide increased resistance by ∼80% and inhibited responses to CGS21680 in control (pEC50=8.3±0.1) and L‐NOARG‐treated hearts (pEC50=7.3±0.1), and to 2‐chloroadenosine in control (pEC50=6.7±0.1) and L‐NOARG‐treated hearts (pEC50=5.9±0.2).
In summary, mouse coronary vessels are more sensitive to adenosine than rat vessels. A2A adenosine receptors mediate dilation in mouse coronary vessels vs A2B receptors in rat. Responses in the mouse involve a sensitive NO‐dependent response and KATP‐dependent dilation.

British Journal of Pharmacology (2001) 133, 1063–1072; doi:10.1038/sj.bjp.0704170
Vascular pharmacology of BIIE0246, the first selective non‐peptide neuropeptide Y Y2 receptor antagonist, in vivo
Authors: Malmström Rickard E 
Published: January 2005

BIIE0246, a recently introduced non‐peptide neuropeptide Y (NPY) Y2 receptor antagonist, was pharmacologically characterized in vivo, on vascular responses evoked in the anaesthetized pig.
The NPY Y2 receptor agonist N‐acetyl[Leu28Leu31]NPY(24‐36) evoked dose‐dependent vasoconstriction in spleen. These vascular responses were potently and dose‐dependently antagonized by BIIE0246. Significant inhibition was seen already at 1 nmol kg−1, whereas at 100 nmol kg−1 of BIIE0246 these responses were completely abolished. The ID50 value for this antagonism was 2.1 nmol kg−1.
Peptide YY (PYY) evoked dose‐dependent vasoconstriction in both kidney and spleen, vascular responses mediated by the NPY Y1 receptor and both NPY Y1 and Y2 receptors, respectively. Only the splenic response was inhibited by BIIE0246, the effect of which reached significance at 1 nmol kg−1. Already 30 min after the last dose of BIIE0246 there was a significant recovery of the PYY‐evoked splenic vasoconstriction, and a further 60 min later, this response was no longer significantly inhibited compared to control.
BIIE0246 (100 nmol kg−1) did not affect renal and splenic vasoconstrictor responses either to the NPY Y1 receptor agonist [Leu31Pro34]NPY, the α1‐adrenoceptor agonist phenylephrine, the P2X1‐purinoceptor agonist α,β‐methylene ATP or angiotensin II, demonstrating both selectivity and specificity for the NPY Y2 receptor in vivo.
It is concluded that BIIE0246 is a highly potent and selective NPY Y2 receptor antagonist, albeit with rather short duration of action, in vivo. BIIE0246 thus represents the first interesting tool for studies on NPY Y2 receptor‐mediated transmission in vivo.

British Journal of Pharmacology (2001) 133, 1073–1080; doi:10.1038/sj.bjp.0704171
2,5‐Di‐t‐butyl‐1,4‐benzohydroquinone (BHQ) inhibits vascular L‐type Ca2+channelviasuperoxide anion generation
Authors: Fusi Fabio , Saponara Simona , Gagov Hristo , Sgaragli Giampietro 
Published: January 2005

The aim of the present study was to investigate the effects of 2,5‐di‐t‐butyl‐1,4‐benzohydroquinone (BHQ), an inhibitor of the sarco‐endoplasmic reticulum Ca2+‐ATPase (SERCA), on the whole‐cell voltage‐dependent L‐type Ca2+current (ICa(L)) of freshly isolated smooth muscle cells from the rat tail artery using the patch‐clamp technique.BHQ, added to the perfusion solution, reduced ICa(L)in a concentration‐ (IC50=66.7 μM) and voltage‐dependent manner. This inhibition was only partially reversible.BHQ shifted the voltage dependence of the steady‐state inactivation curve to more negative potentials by 7 mV in the mid‐potential of the curve, without affecting the activation curve as well as the time course of ICa(L)inactivation.Preincubation of the cells either with 10 μMcyclopiazonic acid, a SERCA inhibitor, or with 3 mMdiethyldithiocarbamate, an inhibitor of intracellular superoxide dismutase (SOD), did not modify BHQ inhibition of ICa(L). On the contrary, this effect was no longer evident when SOD (250 u ml−1) was added to the perfusion medium.Either in the presence or in the absence of cells, BHQ gave rise to superoxide anion formation, which was markedly inhibited by the addition of SOD.These results indicate that, at micromolar concentrations, BHQ inhibits vascular ICa(L)by giving rise to the formation of superoxide anion which in turn impairs the channel function.British Journal of Pharmacology(2001)133, 988–996; doi:10.1038/sj.bjp.0704183
Inactivation of platelet‐derived growth factor‐BB following modification by ADP‐ribosyltransferase
Authors: Saxty Barbara A , Yadollahi‐Farsani Masoud , Upton Paul D , Johnstone Stephen R , MacDermot John 
Published: January 2005

Arginine‐specific ADP‐ribosyltransferase (ART1) is expressed on the surface of a number of cell types, and catalyses the transfer of ADP‐ribose from NAD+ to target proteins. We investigated whether extracellular proteins such as growth factors may serve as substrates for this enzyme, with subsequent alteration in their biological activity. Experiments were performed with rat skeletal muscle membranes and V79 Chinese hamster lung fibroblasts with doxycycline‐inducible expression of human ART.
From a panel of growth factors, platelet‐derived growth factor‐BB (PDGF‐BB) was found to be the best substrate for ART1, whereas the structural homologue PDGF‐AA was not a substrate. Under conditions of maximum labelling 5 mol ADP‐ribose was incorporated per mol of PDGF‐BB.
Purified (ADP‐ribosyl)‐PDGF‐BB did not stimulate a mitogenic or chemotactic response in human pulmonary smooth muscle cells, and showed a reduced capacity to bind to PDGF receptors in competition binding experiments, when compared to unmodified PDGF‐BB.
PDGF‐dependent [3H‐methyl]‐thymidine incorporation was measured in the ART1‐transfected fibroblast cell line at physiological concentrations of PDGF‐BB, and without addition of extracellular NAD+. Fibroblasts expressing human ART1 at the cell surface showed reduced mitogenic responses to PDGF‐BB, but not to PDGF‐AA. This loss of mitogenic response in cells expressing ART1 activity was reversed by the addition of agmatine (an ART1 substrate).
In conclusion, we propose that PDGF‐BB‐dependent signalling may be regulated by post‐translational modification of the growth factor by ART1 at the cell surface. This has been demonstrated in membranes of rat skeletal muscle, and the reaction confirmed in ART1‐transfected fibroblasts.

British Journal of Pharmacology (2001) 133, 1219–1226; doi:10.1038/sj.bjp.0704187
Nebivolol, bucindolol, metoprolol and carvedilol are devoid of intrinsic sympathomimetic activity in human myocardium
Authors: Brixius Klara , Bundkirchen Andreas , Bölck Birgit , Mehlhorn U , Schwinger Robert H G 
Published: January 2005

The present study investigated whether or not there may be differences in the direct cardiac actions of the novel, highly β1‐selective adrenoceptor antagonist nebivolol (NEB) in comparison to metoprolol (MET), bisoprolol (BIS), carvedilol (CAR) and bucindolol (BUC) in human myocardium (n=9).
The rank order of β1‐selectivity as judged by competition experiments to 3H‐CGP 12.1777 in the presence of CGP 207.12 A (300 nmol l−1, Kiβ2) or ICI 118.551 (50 nmol l−1, Kiβ1) were NEB(Kiβ2/Kiβ1: 40.7)>BIS(15.6)>MET(4.23)>CAR(0.73)>BUC(0.49).
The rank order of the negative inotropic potency of the β‐adrenoceptor antagonists measured in left ventricular trabeculae (dilated cardiomyopathy, DCM) as judged by the concentration needed to induce a 50% decrease in isoprenaline (1 μmol l−1)‐stimulated force (IC50) was: MET (0.6 μmol l−1)>CAR (4.1 μmol l−1)>NEB (7.0 μmol l−1).
NEB, BUC, MET and CAR did not not exert an intrinsic sympathomimetic activity (ISA) as determined by measurements of force development in forskolin (0.3 μmol l−1) pre‐treated left ventricular trabeculae, nor by measuring adenylate cyclase activity in forskolin (0.3 μmol l−1)‐stimulated assays (crude membranes). This also holds true for radioligand binding assays with or without guanine nucleotide guanyl‐5′‐yl imidodiphosphate (Gpp(NH)p).
Although all studied β‐adrenoceptor antagonists lack intrinsic sympathomimetic activity (ISA), they differ in the β1‐selectivity as well as in their direct negative inotropic action. These differences as well as the mode of extracardiac action may have an impact on outcome of patients treated with β‐adrenoceptor antagonists.

British Journal of Pharmacology (2001) 133, 1330–1338; doi:10.1038/sj.bjp.0704188