Abstract：
:The discovery of the nitric oxide/cGMP pathway was the basis for our understanding of many normal physiological functions and the pathophysiology of several diseases. Since the discovery and introduction of sildenafil, inhibitors of PDE5 have been the first-line therapy for erectile dysfunction (ED). The success of sildenafil in the treatment of ED stimulated research in the field of PDE5 inhibition and led to many new applications, such as treatment of lower urinary symptoms, and pulmonary arterial hypertension, which are now approved indications. However, PDE5 inhibitors have also been used in several other disorders not discussed in this review, and the fields of clinical use are increasing. In the present review, the pharmacological basis of the NO/cGMP pathway and the rationale and clinical use of PDE5 inhibitors in different diseases are discussed.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Andersson KEdoi
10.1111/bph.14205subject
Has Abstractpub_date
2018-07-01 00:00:00pages
2554-2565issue
13eissn
0007-1188issn
1476-5381journal_volume
175pub_type
杂志文章,评审abstract：:1. Acetylcholine (ACh)-induced relaxation of aortic strips with endothelium and production of cyclic GMP between streptozotocin-induced diabetic and age-matched control rats were compared. 2. The concentration-response curve for ACh-induced relaxation was shifted to the right in diabetic rats. IC50 values for ACh were...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11993.x
更新日期：1989-06-01 00:00:00
abstract：:The effects of injection of 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and N-ethyl-3,4-methylenedioxyamphetamine (MDEA) (all 20 mg kg(-1)) on blood pressure, heart rate, core body temperature and locomotor activity in conscious rats were investigated using radiotelemetry. MDMA and MD...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706688
更新日期：2006-04-01 00:00:00
abstract：:1. This study investigates the effect of partially metabolic controlled long-term (34 weeks) streptozotocin (STZ)-induced diabetes on relaxation and contractile responses of isolated coronary arteries to seven different vasoactive agents. 2. The average fasting and non-fasting blood glucose concentrations (mM) were si...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703159
更新日期：2000-03-01 00:00:00
abstract：:1. In this study we examined the effects of cortistatin, a putative endogenous ligand for somatostatin (SRIF) receptors, on the membrane properties of rat locus coeruleus (LC) neurones in vitro, by use of intracellular and whole cell patch clamp recording. We have compared the actions of cortistatin with those of SRIF...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701541
更新日期：1997-12-01 00:00:00
abstract：:1 The effects of electrical stimulation, changes in external ion concentrations and various drugs on acetylcholine release from the myenteric plexus were measured by bioassay in the presence of physostigmine and by recording the responses of the longitudinal muscle. In preparations from the guinea-pig, the acetylcholi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb17319.x
更新日期：1978-12-01 00:00:00
abstract：:By examination of compound action potentials in the saphenous nerve of the anaesthetized rat it has been shown that capsaicin causes a rapid, dose-dependent, failure of conduction in many C-fibres when applied directly to the nerve. A large reduction in C-fibre conduction occurs with concentrations as low as 110 micro...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10256.x
更新日期：1986-10-01 00:00:00
abstract：:1. The effects of balloon injury on the reactivity of ipsilateral and contralateral carotid arteries were compared to those observed in arteries from intact animals (control arteries). 2. Carotid arteries were obtained from Wistar rats 2, 4, 7, 15, 30 or 45 days after injury and mounted in an isolated organ bath. Reac...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705732
更新日期：2004-05-01 00:00:00
abstract：:1. The aim of the present experiments was to determine whether 5-HT1A receptors play a role in the control of the reflex activation of pulmonary vagal motoneurones. This was carried out by investigating the effects of intracisternal injections (i.c.) of the 5-HT1A receptor ligands, 8-OH-DPAT (50 micrograms kg-1), busp...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15250.x
更新日期：1996-02-01 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. The effects of beta-adrenoceptor blockade on the changes in plasma renin activity (PRA) following angiotensin enzyme (ACE) inhibition were investigated in pentobarbitone-chloralose anaesthetized dogs. 2. ACE-inhibition, with enalapril (2 mg kg-1), caused a significant reduction in systemic arterial blood pressure (...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14338.x
更新日期：1992-06-01 00:00:00
abstract：:1. Antilaminin IgG decreased the dF/dt of mouse isolated atria and inhibited the mechanical effect of acetylcholine in a non-competitive fashion. 2. Inhibitors of nicotinic and muscarinic cholinoceptors impaired the negative inotropic action of antilaminin IgG in mouse isolated atria. Hemicholinium and tetrodotoxin al...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11964.x
更新日期：1989-06-01 00:00:00
abstract：:1. The mechanisms underlying the postjunctional blockade induced by phenthonium [N-(4-phenyl) phenacyl 1-hyoscyamine] were investigated in mammalian and amphibian muscles. This muscarinic antagonist was previously shown to enhance specifically the spontaneous acetylcholine (ACh) release at concentrations that blocked ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701932
更新日期：1998-07-01 00:00:00
abstract：:1. Use of the antihyperglycaemic agent, metformin, is often associated with a small rise in circulating lactate. This study investigates the source of the lactate and examines the effect of metformin on glucose metabolism by the intestine and liver of rats. 2. Changes in plasma glucose and lactate were measured in the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09093.x
更新日期：1992-04-01 00:00:00
abstract：:1. The interaction between the cholinergic and nitrergic innervation was investigated in circular muscle strips of the pig gastric fundus. 2. In physiological salt solution containing 4 x 10(-6) M guanethidine, electrical field stimulation (EFS; 40 V, 0.5 ms, 0.5-32 Hz, 10 s at 4 min intervals) induced small transient...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702244
更新日期：1998-12-01 00:00:00
abstract：:3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') administration to rats produces hyperthermia if they are housed in normal or warm ambient room temperature (Ta) conditions (>or=20 degrees C), but hypothermia when in cool conditions (Ta journal_title：British journal of pharmacology pub_type： 杂志文章 doi：10.1038/sj.bjp.0706318 更新日期：2005-09-01 00:00:00
abstract：:A method is described for the determination of halothane-induced sleeping time in the rat. 2 The sleeping time exhibited a diurnal variation which was due, at least in part, to a change in the sensitivity of the central nervous system (CNS) to the anaesthetic. 3 Tolerance to halothane did not develop in rats repeatedl...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb07689.x
更新日期：1976-09-01 00:00:00
abstract：:1. Adult male rats were treated with propranolol (2.0 mg kg-1 day-1 i.p.), pindolol (0.2 mg kg-1 day-1 i.p.) or 0.9% NaCl day-1 i.p. and exposed to +4 degrees C for 42 days, or treated with 0.9% NaCl day-1 i.p. and kept at +23 degrees C for 42 days. They were weighed once a week, when a 24 h urine sample was also coll...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12988.x
更新日期：1990-04-01 00:00:00
abstract：:1. Endothelin, a novel potent vasoconstrictor peptide produced by vascular endothelial cells stimulated anion secretion by a cultured secretory epithelium derived from the rat epididymis as measured by changes in short-circuit current (SCC). 2. Stimulation of the SCC was observed when endothelin was added to the basol...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12664.x
更新日期：1989-12-01 00:00:00
abstract：:Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings and clinical trials to treat idiopathic pulmonar...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15248
更新日期：2020-09-01 00:00:00
abstract：:1. In order to explore whether 5-HT4 receptor subtypes exist, we have characterized further the 5-HT4 receptor that mediates tachycardia in the piglet isolated right atrium. All experiments were carried out in the presence of propranolol (400 nM) and cocaine (6 microM). We used tryptamine derivatives, substituted benz...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13916.x
更新日期：1993-11-01 00:00:00
abstract：:1 The actions of prostaglandin F2 alpha (PGF2 alpha) and noradrenaline on contraction and 45Ca exchange have been studied in rat mesenteric arteries. 2 PGF2 alpha and noradrenaline contracted rat isolated mesenteric artery preparations to about the same extent. The PGF2 alpha-stimulated contractions, unlike those prod...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb08777.x
更新日期：1982-01-01 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：:1 The effect of clonidine on the 3H-purine release evoked by KCl or (-)-adrenaline was assessed in the superfused helical strip of the rabbit pulmonary artery pretreated with [3H]-adenosine. 2 Clonidine (3 x 10(-5) M to 10(-4) M) significantly enhanced the 3H-purine efflux evoked by 50 mM KCl but not by 3 x 10(-6) M) ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb10482.x
更新日期：1981-11-01 00:00:00
abstract：:Δ9 -tetrahydrocannabinol, the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signalling by binding to cannabinoid CB1 and CB2 receptors on the cell surface. The CB1 receptors are present in both inhibitory and excitatory presynaptic terminals and the CB2 receptors are fo...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14780
更新日期：2019-09-01 00:00:00
abstract：:1. N(G)-monomethyl-L-arginine (L-NMMA) constricts human forearm resistance vasculature and selectively attenuates vasodilator responses to endothelium-dependent vasodilators. Incomplete inhibition of such responses could be due to an inadequate dose of L-NMMA or to NO-independent vasodilator mechanisms. 2. This study ...
journal_title：British journal of pharmacology
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjp.0704338
更新日期：2001-11-01 00:00:00
abstract：:1. Inhalational anaesthetics modulate ligand-gated ion channels at clinical concentrations. In this paper we address submolecular mechanisms for gamma-aminobutyric acid (GABA) receptor modulation by isoflurane. 2. Wild-type Drosophila melanogaster homo-oligomeric GABA receptors were characterized and compared with an ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701417
更新日期：1997-10-01 00:00:00
abstract：:Excessive death of cardiac myocytes leads to many cardiac diseases, including myocardial infarction, arrhythmia, heart failure and sudden cardiac death. For the last several decades, most work on cell death has focused on apoptosis, which is generally considered as the only form of regulated cell death, whereas necros...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14363
更新日期：2019-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:2-Hydroxypropyl-β-cyclodextrin (HPCD) is an FDA approved vehicle for drug delivery and an efficient cholesterol-lowering agent. HPCD was proposed to lower tissue cholesterol via multiple mechanisms including those mediated by oxysterols. CYP27A1 and CYP46A1 are the major oxysterol-producing enzym...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.15209
更新日期：2020-07-22 00:00:00
abstract：:Stimulation of acid secretion by muscarinic cholinomimetic agents depended on the periodic interdigestive activity of the stomach. This explains the peak and following fade. Pentagastrin stimulated gastric secretion after a fixed interval and did not depend on the interdigestive activity. Neither gastrin nor methachol...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb12919.x
更新日期：1985-02-01 00:00:00
abstract：:1. The use of pharmacological inhibitors of nitric oxide (NO) synthesis to treat patients with septic shock is limited by the observation that they cause a fall in cardiac output in some subjects. The aim of this work was to investigate this fall and to test whether it was reversible by subsequent administration of ni...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13089.x
更新日期：1994-06-01 00:00:00
