Abstract:
:1. Pharmacological compounds that release nitric oxide (NO) have been useful tools in the evaluation of the broad role of NO in physiopathology and therapeutics. The present study compared the pharmacokinetics and pharmacodynamics of enalapril and an NO-releasing enalapril molecule (NCX899) in conscious male beagles. The effects of both enalapril and NCX899 in the arterial hypertension and bradycardia induced by acute NO inhibition in anaesthetized dogs were also investigated. 2. Dogs received either NCX899 (4 micromol/kg, i.v.) or enalapril (4 micromol/kg, i.v.), after which plasma concentrations of the analytes and metabolites were quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). 3. In the NCX899 group, the area under the time-course curve (AUC(0-24h)) was 29.18 +/- 4.72, 229.37 +/- 51.32 and 5159.23 +/- 514.88 microg.h/L for the analytes nitro-enalapril, enalapril and enalaprilat, respectively. In the enalapril group, the AUC(0-24h) was 704.53 +/- 158.86 and 4149.27 +/- 847.30 microg.h/L for the analytes enalapril and enalaprilat, respectively. Statistical analysis of data from both groups showed a significant difference for the analyte enalapril, but not for enalaprilat. Moreover, NCX899 and enalapril were equally effective in inhibiting the activity of serum angiotensin-converting enzyme. 4. In anaesthetized dogs, i.v. administration of the NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME; 0.1-10 mg/kg) significantly elevated arterial blood pressure, with concomitant bradycardia. The compound NCX899 significantly attenuated both arterial hypertension and bradycardia, whereas enalapril had no significant effect. 5. In conclusion, the present results showed that the NO-releasing derivative of enalapril NCX899 presents a pharmacokinetic/pharmacodynamic relationship similar to its parent compound enalapril. Moreover, NCX899 (but not enalapril) was effective in protecting against the cardiovascular changes induced by acute NOS inhibition.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Okuyama CE,Mendes GD,Faro R,Rezende VM,Lagos RM,Astigarraga RE,Antunes E,De Nucci Gdoi
10.1111/j.1440-1681.2007.04559.xsubject
Has Abstractpub_date
2007-04-01 00:00:00pages
290-5issue
4eissn
0305-1870issn
1440-1681pii
CEP4559journal_volume
34pub_type
杂志文章abstract::1. Measurements were made on blood pH, PCO2 and PO2 in mice after a single injection and following five weeks continuous clonidine hydrochloride treatment. 2. A single injection of clonidine hydrochloride exerts no effect on blood pH, PCO2 and PO2 but five weeks of continuous clonidine hydrochloride treatment lowers t...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1982.tb00840.x
更新日期:1982-11-01 00:00:00
abstract::The effects of inflammatory changes on the absorption of different-sized probes and their permeability ratios are poorly understood. The aim of the present study was to determine the effects of a pharmacological agent on the permeability of the gut mucosa to saccharidic probes of larger and smaller molecular weight. P...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,随机对照试验
doi:10.1111/1440-1681.12163
更新日期:2014-02-01 00:00:00
abstract::1. The left anterior descending coronary artery (LAD) was completely ligated for 90 min (i.e. myocardial ischaemia was produced) in the dog anaesthetized with pentobarbital. 2. Bevantolol, a beta 1-adrenoceptor antagonist, was injected (1 mg/kg, intravenously) 5 min before LAD occlusion. The bevantolol injection decre...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1991.tb01440.x
更新日期:1991-04-01 00:00:00
abstract::1. Tetramethylpyrazine (TMP) is one of the active principles contained in Ligusticum chuanxiong Hort. (Umbelliferae), a herb that has been used widely in China to treat vascular disorders. 2. In an attempt to elucidate the possible mechanisms of action of TMP, the effect of TMP on intracellular calcium concentrations ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03913.x
更新日期:2003-10-01 00:00:00
abstract::1. The present study examined the cytosolic Ca(2+) regulatory machinery involved in the vasorelaxation produced by petasin, a sesquiterpene isolated from Petasites formosanus. 2. Aortic rings isolated from Sprague-Dawley rats were exposed to petasin (0.01-100 micromol/L) to elucidate its vascular effects on isometric ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2009.05283.x
更新日期:2010-03-01 00:00:00
abstract::Prostaglandin (PG) efflux into ureteral (UE) and venous effluents (VE) of rabbit isolated perfused kidneys was determined by superfusion bioassay and radioimmunoassay (RIA), in response to injections of arginine-vasopressin (AVP), the non-pressor vasopressin analogue 1-deamino-8-D-arginine vasopressin (dDAVP) and arac...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb00942.x
更新日期:1986-08-01 00:00:00
abstract::1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin-induced water reabsorption. 2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subt...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02506.x
更新日期:1994-03-01 00:00:00
abstract::Diabetes is a major risk factor for cardiovascular disease, affecting both endothelial and smooth muscle cells. Store-operated Ca2+ channels (SOCCs) have been implicated in many diabetic complications. Vascular dysfunction is common in patients with diabetes, but the role of SOCCs in diabetic vasculopathy is still unc...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13300
更新日期:2020-07-01 00:00:00
abstract::1. There has been interest in the suggestion that enzyme-inducing drugs, such as anticonvulsants, may produce beneficial changes in lipoprotein levels, in particular a rise in the ratio of high density lipoprotein cholesterol to total cholesterol. 2. This controlled study observed the effects of diets of charcoal or o...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1989.tb01516.x
更新日期:1989-10-01 00:00:00
abstract::1. Ionic channels appear to play an important role in contractile responses of the cerebral arteries and, thereby, contribute to the regulation of cerebral circulation. In the present study, we investigated the role of large-conductance Ca(2+)-activated K+ (BK(Ca)) channels in the regulation of cerebral arterial tone ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2002.03688.x
更新日期:2002-07-01 00:00:00
abstract::1. The use of non-linear dynamic analysis for the measurement of control processes in low-dimensional signals, for example, blood pressure and heart rate variability, are well established and accepted. However, the application of these analytical techniques to a high-dimensional signal, such as renal sympathetic nerve...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1998.tb02340.x
更新日期:1998-11-01 00:00:00
abstract::1. The chronotropic and inotropic effects of the anti-anginal agent SG-75 (2-nicotinamidoethyl nitrate) and 1-verapamil were investigated in isolated blood-perfused canine atrial preparations. The compounds were administered via the cannulated sinus node artery. 2. SG-75 induced a selective negative inotropic as oppos...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1980.tb00062.x
更新日期:1980-03-01 00:00:00
abstract::1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of N...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04482.x
更新日期:2006-11-01 00:00:00
abstract::1. The aim of the present study was to characterize the source of plasma catecholamines induced by centrally administered glucagon-like peptide-1 (GLP-1), with regard to brain prostanoids, in urethane-anaesthetized rats. 2. Glucagon-like peptide-1 and other compounds were administered intracerebroventricularly (i.c.v....
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.04957.x
更新日期:2008-08-01 00:00:00
abstract::1. Ischaemia-reperfusion (IR) injury is an important contributor to tissue damage and has been shown to be attenuated by preconditioning (PC) in some animal models. A recent report has suggested that the forearm can be used for the study of this phenomenon in humans. We aimed to reproduce and further characterize this...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1440-1681.2005.04163.x
更新日期:2005-01-01 00:00:00
abstract::The distribution and binding characteristics of the radioligand (-)-[125I]-cyanopindolol (CYP) have been examined in slide mounted mouse kidney sections, using the technique of in vitro labelling and autoradiography. (-)-[125I]-CYP binding to sections was of high affinity (KD = 55.8 pmol/l, s.e.m. = 8.1, n = 4) to a s...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb00339.x
更新日期:1986-03-01 00:00:00
abstract::1. Plasma concentration and atrial content of atrial natriuretic factor (ANF) were measured in rats with chronic renal failure induced by subtotal nephrectomy. 2. Plasma ANF was higher, and atrial ANF content lower in rats with renal failure when compared with sham-operated controls. 3. Plasma renin activity (PRA) and...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1987.tb00384.x
更新日期:1987-03-01 00:00:00
abstract::Atherosclerosis is a complex chronic inflammatory disease that remains one of the leading causes of death and disability worldwide. A previous study reported that glaucocalyxin A (GLA), a natural ent-Kaurane diterpenoid triptolide, exhibits anti-atherosclerotic activity. However, the underlying molecular mechanism has...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13253
更新日期:2020-05-01 00:00:00
abstract::1. The effects of reserpine pretreatment on neurotransmission in the guinea-pig vas deferens have been re-examined with a view to study the role of noradrenaline (NA) in mediating postjunctional electrical responses and, in particular, excitatory junction potentials (EJP). 2. Reserpine (5 mg/kg, i.p.) caused almost to...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1989.tb01586.x
更新日期:1989-06-01 00:00:00
abstract::1. For the past decade, using radioligand binding, contractility and immunohistochemical techniques, we have been characterizing vascular smooth muscle (VSM) adrenoceptors in four functionally different canine blood vessels, namely the dog aorta (DAO), dog mesenteric artery (DMA), dog mesenteric vein (DMV) and dog sap...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.1999.03136.x
更新日期:1999-10-01 00:00:00
abstract::1. It is known that the alpha(4)-subunit is likely to occur in the brain predominantly in alpha(4)beta(3)delta receptors at extrasynaptic sites. Recent studies have revealed that the alpha(1)-, alpha(4)-, gamma(2)- and delta-subunits may colocalize extrasynaptically in dentate granule cells of the hippocampus. In the ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2010.05374.x
更新日期:2010-07-01 00:00:00
abstract::1. The worldwide epidemic of obesity in adults has been mirrored in children in developed and developing countries. 2. Central obesity appears to be driving a cluster of abnormalities often referred to as the metabolic syndrome. 3. The definition of the metabolic syndrome in children is not suited to arbitrary cut-off...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.04887.x
更新日期:2008-04-01 00:00:00
abstract::The effect of L-thyroxine on serum angiotensin converting enzyme activity using a sheep model was examined. Following two weeks of L-thyroxine treatment, the activity of serum angiotensin converting enzyme was increased from 6.92 U/ml to 8.65 U/ml (s.e.m. = 0.40, n = 13, P less than 0.01). Discontinuation of L-thyroxi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb00945.x
更新日期:1986-08-01 00:00:00
abstract::1. Poor perfusion of the kidneys and gut, and associated functional impairment, are major problems in the first days of life in very preterm infants. These complications can be associated with a substantial mortality and further problems such as reduced kidney growth and chronic renal problems in later childhood. 2. T...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2006.04364.x
更新日期:2006-04-01 00:00:00
abstract::1. The diffusional permeability of collecting ducts to 22Na+ and 36Cl- was measured in rat papillae in vitro. 2. The permeability of the collecting duct to 36Cl- was 0.72 (s.e.m. = 0.01; n = 356) microns/sec which was significantly higher than the value of 0.51 (s.e.m. = 0.01; n = 356) microns/sec measured for 22Na+. ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1982.tb00837.x
更新日期:1982-11-01 00:00:00
abstract::1. Angiotensin (Ang)II is involved in responses to hypovolaemia, such as sodium appetite and increase in blood pressure. Target areas subserving these responses for AngII include the cardiovascular system in the periphery and the circumventricular organs in the brain. 2. Conflicting data have been reported for the rol...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2000.03262.x
更新日期:2000-05-01 00:00:00
abstract::1. Pericytes are cells of microvessels (arterioles, capillaries and venules) that wrap around endothelial cells. They are most abundant on venules and are common on capillaries. 2. The pericyte population is highly variable between different tissues and organs, probably in a manner reflecting postarteriolar hydrostati...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2000.03343.x
更新日期:2000-10-01 00:00:00
abstract::Asymmetric dimethylarginine (ADMA) is an endogenously produced nitric oxide synthase (NOS) inhibitor. L-Arginine can be metabolised by NOS and arginase, and arginase is the first step in polyamine production necessary for cellular proliferation. We tested the hypothesis that ADMA would inhibit NOS but not arginase act...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12252
更新日期:2014-07-01 00:00:00
abstract::1. The aim of the present study was to evaluate the clinical value of colour Doppler application in encircling constriction of the superficial femoral vein in deep vein insufficiency. 2. A total of 87 patients with primary deep venous insufficiency (PDVI) using ascending venography were randomly divided into group A (...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1440-1681.2011.05620.x
更新日期:2011-12-01 00:00:00
abstract::1. In the present study we have examined the effects of angiotensin I converting enzyme (ACE) inhibition and nitric oxide (NO) synthesis inhibition on bradykinin (BK) depressor responses in pregnancy in both Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. Ramipril (10 mg/kg, i.v.) significantly reduce...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1995.tb02051.x
更新日期:1995-06-01 00:00:00