Abstract:
:1. In a first series of experiments, male Long Evans rats were chronically instrumented for the measurement of internal carotid blood flow and systemic arterial blood pressure; cardiovascular changes were assessed during and after 30 min infusions of human alpha-calcitonin gene-related peptide (CGRP) (0.06 and 0.6 nmol h-1), or nimodipine (60 and 600 nmol h-1) or human alpha-CGRP plus nimodipine. The effects of human alpha-CGRP or nimodipine on internal carotid vasoconstriction induced by endothelin-1 were also measured. 2. Human alpha-CGRP (0.06 nmol h-1) caused a small (+15%), transient increase in internal carotid blood flow and a tachycardia (+33 beats min-1), but no change in mean blood pressure. Nimodipine (60 nmol h-1) caused a brief internal carotid hyperaemia (+16%) but no changes in blood pressure or heart rate. However, concurrent administration of human alpha-CGRP (0.06 nmol h-1) and nimodipine (60 nmol h-1) caused a sustained increase in internal carotid blood flow (+40%) unaccompanied by significant changes in heart rate or blood pressure. 3. Human alpha-CGRP at a dose of 0.6 nmol h-1 or nimodipine at a dose of 600 nmol h-1 caused substantial reductions in internal carotid vascular resistance (-43 and -40%, respectively); concurrent administration of these doses did not have an additive vasodilator effect. 4. Infusion of endothelin-1 (1.2nmolhV1) for 20min caused incremental constriction of the internal carotid vascular bed; human alpha-CGRP infusion (0.6 and 6.0nmolh-1) begun tOmin after the onset of endothelin-1 infusion reversed this effect (dose-dependently); nimodipine (600nmolh-1) also caused a substantial attenuation of the effects of endothelin-1. 5. In a second series of experiments the haemodynamic effects of human alpha-CGRP and/or nimodipine were assessed in rats chronically instrumented for the measurement of renal, superior mesenteric and hindquarters blood flow together with systemic arterial blood pressure. 6. Administration of human alpha-CGRP (0.06 nmol h-') alone or in conjuction with nimodipine (60nmolh-1) had no significant effects on renal or superior mesenteric vascular resistances, although there was a slight hindquarters vasodilatation. Human alpha-CGRP at a dose of 0.6 nmol -1 caused hypotension, tachycardia and reductions in renal and superior mesenteric blood flows, together with a marked (+31% maximum) hindquarters hyperaemia. Nimodipine at a dose of 600 nmol h-1 caused hypotension, tachycardia and a reduction (-34%) in renal blood flow; mesenteric blood flow was unchanged and there was an increase in hindquarters flow (+ 59%). 7. Concurrent administration of human alpha-CGRP (0.6 nmol h 1) and nimodipine (600 nmol h') did not have an additive hypotensive effect or an enhanced hindquarters hyperaemic effect, but was associated with a marked impairment of renal blood flow (-48%). 8. The present results indicate that concurrent administration of low doses of human alpha-CGRP and nimodipine might be particularly helpful in the acute treatment of patients with cerebral vasospasm and impaired renal perfusion, since this intervention improved internal carotid blood flow without compromising blood flow to the kidney.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Gardiner SM,Compton AM,Bennett T,Kemp PA,Ney Udoi
10.1111/j.1476-5381.1990.tb13015.xsubject
Has Abstractpub_date
1990-04-01 00:00:00pages
830-4issue
4eissn
0007-1188issn
1476-5381journal_volume
99pub_type
杂志文章abstract::1. The inhibitory transmission in isolated preparations of cavernosal smooth muscle from human penis has been studied. 2. Electrical field stimulation (EFS; 2-64 pulses/train, 0.8 ms pulse duration, 10 Hz) evoked relaxation of preparations treated with guanethidine (50 microM). The EFS-evoked relaxations were atropine...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12500.x
更新日期:1991-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:A putative novel cannabinoid receptor mediates vasorelaxation to anandamide and abnormal-cannabidiol and is blocked by O-1918 and by high concentrations of rimonabant. This study investigates VSN16, a novel water-soluble agonist, as a vasorelaxant potentially acting at non-CB1, non-CB2 cannabinoi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707470
更新日期:2007-11-01 00:00:00
abstract::1. Calcium entry via neuronal calcium channels is essential for the process of neurotransmission. We investigated the calcium channel subtypes involved in the operation of cardiac autonomic neurotransmission by examining the effects of selective calcium channel blockers on the inotropic responses to electrical field s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702629
更新日期:1999-06-01 00:00:00
abstract::1. In the neuronally isolated cortex of the cat, local application of bemegride, picrotoxin, nikethamide, caffeine and strychnine facilitated the surface positive response of the isolated cortex and lowered the stimulus threshold for this response. Excepting nikethamide, they all produced convulsive discharge in the i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09897.x
更新日期:1970-08-01 00:00:00
abstract::AM-36 is a novel neuroprotective agent incorporating both antioxidant and Na(+) channel blocking actions. In cerebral ischaemia, loss of cellular ion homeostasis due to Na(+) channel activation, together with increased reactive oxygen species (ROS) production, are thought to contribute to neuronal death. Since neurona...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704018
更新日期:2001-04-01 00:00:00
abstract::1. The purpose of this investigation was to determine whether enhanced contractile responses to noradrenaline (NA) of mesenteric arteries from rats with chronic streptozotocin-induced diabetes are associated with increases in mean cytosolic [Ca(2+)]i. 2. [Ca(2+)]i was measured with fura 2-AM, and was monitored simulta...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704221
更新日期:2001-09-01 00:00:00
abstract::Histamine-induced contractions of small airways from human lung were substantially augmented by the cyclo-oxygenase inhibitor, indomethacin, whereas the contraction of larger airways was not. Mixed cyclo-oxygenase/lipoxygenase inhibitors of arachidonic acid metabolism did not modify histamine-induced contractions of s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09333.x
更新日期:1982-12-01 00:00:00
abstract::The effects of verapamil on the contraction of the guinea-pig tracheal smooth muscle induced by calcium (Ca2+) or barium (Ba2+) were investigated in three different conditions: (a) in excess K solution, (b) in the presence of carbachol, and (c) in excess K solution containing carbachol. In order to clarify the contrac...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10222.x
更新日期:1986-06-01 00:00:00
abstract::In the last 20 years, the global regulatory frameworks for drug assessment have been managing the challenges posed by using cellular products as new therapeutic tools. Currently, they are defined as "Advanced Therapy Medicinal Products", comprising a large group of cellular types that either alone or in combination wi...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15305
更新日期:2020-11-03 00:00:00
abstract::The pharmacological activity of two natural bombesin-like peptides, alytesin and litorin, and 25 related synthetic peptides has been compared to that of bombesin. 2 The minimum length of the amino acid chain required for the first appearance of bombesin-like effects was represented by the C-terminal heptapeptide, and ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07631.x
更新日期:1975-10-01 00:00:00
abstract::By implanting a Teflon chamber subcutaneously into a sheep a mild aseptic inflammatory lesion was produced from which wound fluid could be sampled daily. The prostaglandin content of this wound fluid was examined. Prostaglandin E2 activity was found in all samples, and a peak was apparent on the fourth or fifth day af...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07363.x
更新日期:1975-02-01 00:00:00
abstract::1. Behavioural activity (delayed differentiation and spatial delayed alternation) and pharmacokinetics of diazepam and its metabolites, N-desmethyldiazepam (nordiazepam), 3-hydroxydiazepam (temazepam) and 3-hydroxy-N-desmethyldiazepam (oxazepam), and of dipotassium clorazepate (clorazepate), were studied in the monkey...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08423.x
更新日期:1977-11-01 00:00:00
abstract::1. Dopamine efflux following single pulse or train of pulse stimulations was measured in slices of rat caudate putamen, nucleus accumbens and tuberculum olfactorium, using fast cyclic voltammetry at a carbon fibre microelectrode; 1, 5, 10, 20 or 50 pulses were applied at each location at frequencies varying from 10 Hz...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14355.x
更新日期:1992-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Dexpramipexole, a drug recently tested in patients with amyotrophic lateral sclerosis (ALS,) is able to bind F1Fo ATP synthase and increase mitochondrial ATP production. Here, we have investigated its effects on experimental ischaemic brain injury. EXPERIMENTAL APPROACH:The effects of dexpramipe...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13790
更新日期:2018-01-01 00:00:00
abstract::The cardiovascular actions of cannbinoids are complex. In general they cause vasorelaxation in isolated blood vessels, while in anaesthetised animals they cause multiphasic responses which involve an early bradycardia and long-lasting hypotension. However, in conscious animals, the picture is one of bradycardia follow...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0705725
更新日期:2004-05-01 00:00:00
abstract::1. Pressor responses to sympathetic outflow stimulation, noradrenaline and angiotensin have been recorded in pithed rats.2. Disulfiram (50 mg/kg) and sodium diethyldithiocarbamate (DDC) (5-100 mg/kg) both caused an initial increase in the pressor response to all three procedures followed by a selective inhibition of t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb07255.x
更新日期:1972-02-01 00:00:00
abstract::1 Endothelin-1 (ET-1), an endothelium-derived vasoactive peptide, participates in the regulation of endothelial function through mechanisms that are not fully elucidated. This study examined the impact of ET-1 on oxidative stress, apoptosis and cell proliferation in human umbilical vein endothelial cells (HUVEC). HUVE...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706193
更新日期:2005-06-01 00:00:00
abstract::In the rabbit isolated pulmonary artery, neither the ETA receptor antagonist, BQ-123 (10 microM), nor the ETB receptor antagonist, BQ-788 (10 microM), inhibited the contractions induced by 1 nM endothelin-1 (ET-1). However, the combination of BQ-123 and BQ-788 completely inhibited the ET-1-induced contraction. In cont...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb16901.x
更新日期:1994-10-01 00:00:00
abstract::1. Daily i.p. administration, for eight days, of the cholinesterase inhibitor disulfoton to rats produced mild to moderate signs of intoxication (tremors, incontinence and diarrhoea) but no deaths.2. Segments of ileum taken from the treated rats were subsensitive to carbachol but the vas deferens and the uterus did no...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08350.x
更新日期:1973-07-01 00:00:00
abstract::1. Calcium channel blockers increase cardiovascular morbidity and mortality in patients with left ventricular dysfunction. These adverse effects are probably related to the negative inotropic effect of calcium channel blockers and/or a neurohormonal activation. 2. The present study was designed to examine, in consciou...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17002.x
更新日期:1994-10-01 00:00:00
abstract::1. We have investigated the effects of a standardised mixture of hydroxyethylrutosides (HR, Venoruton), a mixture of five of its main components (M) and each of the five components separately (7-mono-HR, 7,4'-di-HR, 7,3',4'-tri-HR, 5,7,3',4'-tetra-HR and 7,3'4'-tri HQ) upon the permeability of single perfused capillar...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13792.x
更新日期:1993-09-01 00:00:00
abstract::1. Histamine contracted the tracheal and major bronchial muscles of sheep and relaxed the muscles of the lesser bronchi and bronchioles.2. The stimulant action of histamine on the trachea was antagonized by mepyramine, whereas the relaxant effect on the bronchial tree was not.3. 5-Hydroxytryptamine contracted the musc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb07997.x
更新日期:1969-07-01 00:00:00
abstract::In circular smooth muscle cells of the guinea-pig stomach (antrum), diltiazem (10(-6)-10(-5)M) blocked the overshooting spike potential generated either spontaneously or by electrical stimulation in the presence of 2 mM tetraethylammonium chloride, but did not block the slow wave and the abortive spike potential. The ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb11100.x
更新日期:1985-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Rho kinase (ROCK) activation is involved in neuroinflammatory processes leading to progression of neurodegenerative diseases such as Parkinson's disease. Furthermore, ROCK plays a major role in angiogenesis. Neuroinflammation and angiogenesis are mechanisms involved in developing l-DOPA-induced d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15275
更新日期:2020-12-01 00:00:00
abstract::1. The effects of propentofylline (PPF, 25 mg kg(-1) body weight per day) on rat cerebral energy state and cytokine expression as well as on behaviour and histopathology were studied after acute and long-term permanent bilateral common carotid artery occlusion (BCCAO). 2. In the absence of PPF, acute ischaemia led to ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704061
更新日期:2001-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707219
更新日期:2007-05-01 00:00:00
abstract::At nanomolar concentrations, SR141716 and AM251 act as specific and selective antagonists of the cannabinoid CB1 receptor. In the micromolar range, these compounds were shown to inhibit basal G-protein activity, and this is often interpreted to implicate constitutive activity of the CB1 receptors in native tissue. We ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705577
更新日期:2003-12-01 00:00:00
abstract::1. Electrical stimulation of the mid-brain raphé in anaesthetized adrenalectomized rats produced a significant decrease in the forebrain content of 5-hydroxytryptamine (5-HT) and an increase in the concentration of 5-hydroxyindol-3-ylacetic acid (5-HIAA).2. Stimulation of peripheral sensory nerves did not influence ei...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09550.x
更新日期:1970-05-01 00:00:00
abstract::1 This study investigated the effects of soluble complement receptor type 1 (sCR1) or sCR1sLex, agents which function as a complement inhibitor or as a combined complement inhibitor and selectin adhesion molecule antagonist, respectively, on the infarct size and cardiac troponin T (cTnT) release caused by regional myo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702889
更新日期:1999-11-01 00:00:00
abstract::1. In this study 3 protocols were utilized to determine the role of endogenous kinins in the resistance of the inbred Dahl (Rapp) salt-resistant (SR/Jr) rats to high salt diet-induced blood pressure elevation. 2. The bradykinin B2 receptor antagonist, Hoe 140 (D-Arg[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin) at doses of ei...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701797
更新日期:1998-05-01 00:00:00