Abstract:
:1. The systemic and regional haemodynamic effects of the potassium channel activator EMD 52692 or its solvent were investigated after intravenous and after intracoronary administration in anaesthetized pigs. 2. Consecutive intravenous 10 min infusions of EMD 52692 (0.15, 0.30, 0.60, 1.20 micrograms kg-1 min-1; n = 7) dose-dependently decreased mean arterial blood pressure by up to 50%. This was entirely due to peripheral vasodilatation, since cardiac output did not change. Heart rate increased by up to 50%, while left ventricular end diastolic pressure decreased dose-dependently from 6 +/- 1 mmHg to 3 +/- 1 mmHg (P less than 0.05), and stroke volume decreased from 30 +/- 2 ml to 21 +/- 2 ml (P less than 0.05). Left ventricular dP/dtmax was not affected. 3. Although cardiac output did not change, EMD 52692 caused a redistribution of blood flow from the arteriovenous anastomoses to the capillary channels. Blood flow to the adrenals, small intestine, stomach, bladder, spleen and brain increased, while renal blood flow decreased and blood flow to several muscle groups and skin were not altered. Vascular conductance was increased dose-dependently in all organs, except for the kidneys, where after the initial increase, vascular conductance returned to baseline with the highest dose. Particularly striking were the effects on the vasculature of the brain. With the highest dose of EMD 52692 blood flow more than doubled, while vascular conductance increased four fold. 4. Transmural myocardial blood flow increased slightly, which was entirely due to an increase in subepicardial blood flow. Myocardial O2-consumption and segment length shortening were not significantly affected. 5. After consecutive 10 min intracoronary infusions (0.0095, 0.019, 0.0375 and 0.075 microgram kg-1 min-1; n = 7) into the left anterior descending coronary artery (LADCA), mean arterial blood pressure was maintained with the lowest two doses, but decreased by up to 15% with the higher doses, whereas heart rate increased by up to 24%. Blood flow to the LADCA-perfused myocardium doubled with the highest dose, the subepicardium benefitting the most. Coronary venous O2-saturation increased dose-dependently from 23 +/- 2% to 60 +/- 4%, while myocardial O2-consumption of the LADCA-perfused myocardium was not affected by the drug. 6. It is concluded that EMD 52692 is a potent vasodilator, with particularly pronounced effects on vasculature of the brain. Its selectivity for vascular smooth muscle cells exceeds that for the myocytes, since with doses that are much higher than those of potential clinical interest no negative inotropic effects were observed. The compound primarily dilates arteries but some venodilatation may also occur.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Sassen LM,Duncker DJ,Gho BC,Diekmann HW,Verdouw PDdoi
10.1111/j.1476-5381.1990.tb14128.xsubject
Has Abstractpub_date
1990-11-01 00:00:00pages
605-14issue
3eissn
0007-1188issn
1476-5381journal_volume
101pub_type
杂志文章abstract::1. The effects of lifarizine (RS-87476) on intracellular Ca2+ rises and the release of glutamate from rat cerebrocortical synaptosomes depolarized with 30 mM KCl were investigated by use of entrapped fura 2 and exogenous glutamate dehydrogenase. 2. Prior (1 min) addition of lifarizine decreased 30 mM KCl-induced total...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15380.x
更新日期:1996-05-01 00:00:00
abstract::1. The effects of adrenaline, noradrenaline, isoprenaline and terbutaline (PINN), 1-(3,5-dihydroxyphenyl)-2(t-butylamino)-ethanol, on the sphincter of Oddi were studied in anaesthetized cats. Both adrenaline and noradrenaline (1-4 mug/kg) increased resistance to flow through the sphincter. This effect was blocked by d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb10369.x
更新日期:1970-07-01 00:00:00
abstract::1. The effect of prolonged anti-hypertensive drug treatment on the blood pressure of conscious spontaneously hypertensive rats (SH-rats), and of age-matched normotensive Sprague-Dawley rats was determined during the development of hypertension in SH-rats and in the early stages of established hypertension. A compariso...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07588.x
更新日期:1975-08-01 00:00:00
abstract::Monocytes and macrophages provide key targets for the action of novel anti-inflammatory therapeutics targeted at inhibition of PDE4 cAMP-specific phosphodiesterases. PDE4 enzymes provide the dominant cAMP phosphodiesterase activity in U937 human monocytic cells. Differentiation of U937 monocytic cells to a macrophage-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705770
更新日期:2004-05-01 00:00:00
abstract::1. Aqueous extracts of stratum corneum were found to cause histamine-like contractions of the guinea-pig ileum which were not antagonized by mepyramine, atropine or bromolysergic acid diethylamide.2. The compounds responsible for this contraction were isolated by chromatography and shown to be common amino acids, part...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb09581.x
更新日期:1972-05-01 00:00:00
abstract::A large range of neuroadaptations develop in response to chronic opioid exposure and these are thought to be more or less critical for expression of the major features of opioid addiction: tolerance, withdrawal and processes that may contribute to compulsive use and relapse. This review considers these adaptations at ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/bjp.2008.100
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Cytochrome P450 (CYP, P450) 3A4 is involved in the metabolism of 50% of drugs and its catalytic activity in vivo is not explained only by hepatic expression levels. We previously demonstrated that UDP-glucuronosyltransferase (UGT) 2B7 suppressed CYP3A4 activity through an interaction. In the pres...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14900
更新日期:2020-03-01 00:00:00
abstract::1. Prostaglandin F2 alpha (PGF2 alpha) and its synthetic analogue, fluprostenol, potently relaxed the precontracted isolated jugular vein of the rabbit (RJuV). The vasorelaxant activity of PGF2 alpha and fluprostenol was dependent upon an intact vascular endothelium. Although removal of the vascular endothelium abolis...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15960.x
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The chemokine receptor CXCR3 directs migration of T-cells in response to the ligands CXCL9/Mig, CXCL10/IP-10 and CXCL11/I-TAC. Both ligands and receptors are implicated in the pathogenesis of inflammatory disorders, including atherosclerosis and rheumatoid arthritis. Here, we describe the molecul...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01660.x
更新日期:2012-06-01 00:00:00
abstract::1 The mechanism underlying the enhancement by superoxide dismutase (SOD) of endothelium-dependent relaxation was investigated in rabbit mesenteric resistance arteries. 2 SOD (200 U ml(-1)) increased the production of H(2)O(2) in smooth muscle cells (as indicated by the use of an H(2)O(2)-sensitive fluorescent dye). 3 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705255
更新日期:2003-05-01 00:00:00
abstract::1. The effects of several agonists of the metabotropic glutamate receptor (mGluR) were studied in adult rat striatal slices by measuring (i) KCl (30 mM)-induced output of previously taken up D-[3H]-aspartate (Asp), (ii) forskolin (30 microM)-induced adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation and (i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13977.x
更新日期:1993-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:SU4312, a potent and selective inhibitor of VEGF receptor-2 (VEGFR-2), has been designed to treat cancer. Recent studies have suggested that SU4312 can also be useful in treating neurodegenerative disorders. In this study, we assessed neuroprotection by SU4312 against 1-methyl-4-phenylpyridinium ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12004
更新日期:2013-03-01 00:00:00
abstract::1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50-70 times less active than bradykinin on the guinea-pig ileum and 70-160 times less active on isolated strips of cat terminal ileum. 3 The action of b...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb06985.x
更新日期:1977-01-01 00:00:00
abstract::1. Possible interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and endogenous opioids were examined in electrophysiological experiments in alpha-chloralose anaesthetized spinalized rats without or with carrageenan-induced acute inflammation of one hindpaw. Spinal reflex responses, monitored as single ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15494.x
更新日期:1996-06-01 00:00:00
abstract::The effect of a substance P antagonist, [D-Pro2, D-Trp7,9]-substance P (SPA), on gastric emptying and gastrointestinal transit in the rat was studied in order to elucidate a possible physiological role of endogenous substance P and other tachykinins in gastrointestinal motility. SPA was given by intraperitoneal inject...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb11144.x
更新日期:1986-11-01 00:00:00
abstract::1. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective anti-inflammatory and analgesic drugs although they also induce unwanted side effects due to the inhibition of the physiological effects regulated by prostaglandins. This has led to the search for new compounds with fewer side effects, such as the nitro-N...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704589
更新日期:2002-03-01 00:00:00
abstract::1. Using a guinea-pig model of allergic asthma, we investigated the role of L-arginine limitation in the allergen-induced deficiency of nitric oxide (NO) and airway hyperreactivity (AHR) after the early asthmatic reaction, by examining the effects of various concentrations of the NO synthase (NOS) substrate on the res...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702882
更新日期:1999-11-01 00:00:00
abstract::Ryanodine (1 microM) suppressed or abolished contraction in response to step depolarization in voltage-clamped cells isolated from adult rat ventricular myocardium. The step depolarizations evoked the second inward current, which is carried largely by Ca ions under these conditions, and there was little or no change i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10735.x
更新日期:1984-01-01 00:00:00
abstract::1. Intrathecal (i.t.) injection of nociceptin at small doses (fmol order) elicited a behavioural response consisting of scratching, biting and licking in conscious mice. Here we have examined the involvement of substance P-containing neurons by using i.t. injection of tachykinin neurokinin (NK)1 receptor antagonists a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702698
更新日期:1999-08-01 00:00:00
abstract::1. Inhibition of rat platelet aggregation by the nitric oxide (NO) donor MAHMA NONOate (Z-1-N-methyl-N-[6-(N-methylammoniohexyl)amino]diazen-1-ium-1,2-diolate) was investigated. The aims were to compare its anti-aggregatory effect with vasorelaxation, to determine the effects of the soluble guanylate cyclase inhibitor...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704971
更新日期:2002-12-01 00:00:00
abstract::Measurements of affinity and efficacy are fundamental for work on agonists both in drug discovery and in basic studies on receptors. In this review I wish to consider methods for measuring affinity and efficacy at G protein coupled receptors (GPCRs). Agonist affinity may be estimated in terms of the dissociation const...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707672
更新日期:2008-04-01 00:00:00
abstract::1. Human big-endothelin-1 (big-ET-1) and endothelin-1 (ET-1) are equipotent as pressor agents and produce a significant change in mean arterial blood pressure (MAP) in anaesthetized guinea-pigs (2 nmol kg-1: peak delta MAP: 23 +/- 6 mmHg and 26 +/- 5 mmHg, respectively). 2. Unlike big-ET-1, big-endothelin-3 (big-ET-3)...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12448.x
更新日期:1991-10-01 00:00:00
abstract::1. The vasodilator responses of isolated intrapulmonary arteries (IPA) to P2-receptor agonists were investigated during adaptation to extrauterine life in the piglet. The effect of pulmonary hypertension on the normal response was determined after exposing newborn animals to chronic hypobaric hypoxia (51 kPa) for 3 da...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702815
更新日期:1999-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pancreatic islet transplantation is a promising therapeutic approach for Type 1 diabetes. A major prerequisite for the survival of grafted islets is a rapid revascularization after transplantation. Erythropoietin (EPO), the primary regulator of erythropoiesis, has been shown to promote angiogenes...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14925
更新日期:2020-04-01 00:00:00
abstract::1. Previous patch clamp studies of oesophageal circular muscle cells showed that nitric oxide (NO) modulated the opening of Ca2(+)-activated K+ channels involved in mediating the inhibitory junction potentials (i.j.ps). This study clarified the role of Ca2+ release from the superficial sarcoplasmic reticulum (SR) in t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15661.x
更新日期:1996-08-01 00:00:00
abstract::For almost three decades intrathecal baclofen therapy has been the standard treatment for spinal cord injury spasticity when oral medication is ineffective or produces serious side effects. Although intrathecal baclofen therapy has a good clinical benefit-risk ratio for spinal spasticity, tolerance and the life-threat...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
doi:10.1111/j.1476-5381.2010.00964.x
更新日期:2010-11-01 00:00:00
abstract::1. Recently we and others have demonstrated a stereoselective inhibition of slowly activating human I(Ks) (KCNQ1/MinK) and homomeric KCNQ1 potassium channels by the enantiomers of the chromanol 293B. Here, we further characterized the mechanism of the 293B block and studied the influence of the 293B enantiomers on the...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704421
更新日期:2001-12-01 00:00:00
abstract::1 The effect of 5-hydroxytryptamine (5-HT) on acid secretion by a rat isolated stomach preparation has been studied. 2 5-HT at 10(-5)M in the serosal bathing fluid produced significant inhibition of the acid secretory responses to histamine, pentagastrin and isoprenaline but was without effect on basal secretion or th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb09371.x
更新日期:1983-01-01 00:00:00
abstract::Ginsenoside Rg3 (Rg3) isolated from Panax ginseng relaxes vessels and exerts a cytoprotective effect. In view of the fact that nitric oxide (NO) is involved in vascular hyporeactivity and immunostimulation, the effects of total ginsenosides (GS) and Rg3 on the vascular responses and the expression of inducible nitric ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705490
更新日期:2003-10-01 00:00:00
abstract::1. A biliary fistula was prepared in twelve sheep.2. Each animal was given 2 ml. of (14)C-carbon tetrachloride (specific activity 15 mc/m-mole) and bile collected at 2, 4, 24 and 48 hr.3. Specific activity was measured by liquid scintillation counting before and after each specimen had been heated to 75 degrees C for ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb09502.x
更新日期:1969-06-01 00:00:00