Abstract:
:1. Combined treatment of spontaneously hypertensive rats (SHR) with AT1 receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors has been shown to reduce mean arterial pressure (MAP) more than monotherapy with either agent. The aims of the present study were to investigate the effects of chronic dual renin-angiotensin system (RAS) inhibition using non-hypotensive doses of the AT1 receptor antagonist candesartan cilexetil and the ACE inhibitor perindopril on cardiovascular function and structure. 2. Adult male SHR, aged 15 weeks, were divided into four groups: (i) candesartan cilexetil (0.5 mg/kg per day in drinking water); (ii) perindopril (0.3 mg/kg per day in drinking water); (iii) combined treatment (dual RAS inhibition); or (iv) the appropriate vehicle (0.1% ethanol/0.1% polyethylene glycol/1.5 mmol/l sodium bicarbonate dissolved in water for candesartan cilexetil; distilled water for perindopril). Systolic blood pressure was measured weekly using the tail-cuff method and urinary microalbuminuria was measured fortnightly. 3. After 4 weeks, rats were instrumented for intravenous drug administration and measurement of MAP. At this time, the cardiovascular effects of angiotensin (Ang) I and AngII (5-20 ng) and sodium nitroprusside (SNP) and acetylcholine (ACh; 1-5 micro g) were assessed. In addition, left ventricular : bodyweight and media : lumen ratios were determined as indices of cardiac and vascular hypertrophy, respectively. 4. Candesartan cilexetil and perindopril alone had minimal effect on MAP when measured both directly and indirectly, whereas direct MAP was significantly decreased in the combined treatment group (131 +/- 6 mmHg; P < 0.05) compared with the vehicle group (156 +/- 9 mmHg). Pressor responses to AngI were significantly decreased in all groups compared with the vehicle-treated group and pressor responses to AngII were significantly decreased in the candesartan cilexetil-treated (P < 0.01) and combined treatment groups (P < 0.01) compared with the vehicle-treated group. Depressor responses to ACh and SNP were not significantly affected by any of the antihypertensive therapies compared with vehicle-treated SHR. 5. Vascular hypertrophy was significantly decreased in the candesartan cilexetil and combined groups compared with the vehicle-treated group, whereas cardiac hypertrophy was reduced, with the rank order of effect being: dual RAS inhibition > perindopril > candesartan cilexetil. Urinary albumin tended to decrease with dual RAS inhibition, but was not significantly affected by this short-term treatment. 6. These results demonstrate the efficacy of low-dose dual RAS inhibition as an antihypertensive modality, at least in SHR, not only in reducing arterial pressure, but also in improving cardiovascular structure.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Duke LM,Paull JR,Widdop REdoi
10.1046/j.1440-1681.2003.03837.xkeywords:
subject
Has Abstractpub_date
2003-05-01 00:00:00pages
317-23issue
5-6eissn
0305-1870issn
1440-1681pii
3837journal_volume
30pub_type
杂志文章abstract::Responses of the toad isolated rectus abdominis muscle to cumulative doses of carbachol were recorded in the absence or presence of varying concentrations of cimetidine or ranitidine. The corresponding cumulative log concentration-response curves for carbachol were then plotted for each antagonist studied. Cimetidine ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb00946.x
更新日期:1986-08-01 00:00:00
abstract::1. Insulin-like growth factor (IGF)-I has acute effects on cardiovascular function, including a well-characterized vasodilator response in isolated arteries. In addition to increasing the release of nitric oxide, IGF-I also has effects on a variety of other signalling pathways that affect vascular tone, in particular ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04510.x
更新日期:2006-12-01 00:00:00
abstract::1. Angiotensin (Ang) II causes growth-related effects on vascular smooth muscle cells in vitro and in vivo. 2. Chronic infusions of AngII systemically, at doses that are initially subpressor, result in slowly progressive increases in arterial pressure ('slow-pressor' hypertension). It has been suggested that the hyper...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03590.x
更新日期:2001-12-01 00:00:00
abstract::The kidney has a unique environment that results in relatively low tissue oxygen tension (Po2). However, recent studies have shown that renal hypoxia is more severe during hypertension and may reflect changes in the way O2 is used. The present review summarizes studies that explore the relationship between renal oxyge...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2006.04478.x
更新日期:2006-10-01 00:00:00
abstract::1. (-)[125I]-Cyanopindolol (CYP) binding to non-beta-adrenoceptor sites in dog kidney was characterized in homogenate preparations and their distribution in sections determined using autoradiography. 2. In homogenate studies, (-)[125I]-CYP bound to a single population of non-interacting sites (Bmax = 5.45, s.e.m. = 1....
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1987.tb01896.x
更新日期:1987-09-01 00:00:00
abstract::1. Cardiovascular events and outcome in septic shock may be predicted by monitoring the fall in intramural pH (pHi), as an index of splanchnic perfusion and mucosal ischaemia. In the present study, a small animal model for monitoring the changes of gastric pHi or intramucosal [H+] following challenge with the endotoxi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03432.x
更新日期:2001-03-01 00:00:00
abstract::1. The aim of the present study was to investigate the mechanism underlying biochanin A-induced relaxation of the aorta in spontaneously hypertensive rats (SHR). 2. The tension in isolated ring preparations of thoracic aortas from normotensive (Wistar-Kyoto (WKY) rats) and SHR at 5 and 10 weeks of age was measured iso...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04443.x
更新日期:2006-09-01 00:00:00
abstract::Ageing is associated with increased prevalences of both atrial and ventricular arrhythmias, reflecting disruption of the normal sequence of ion channel activation and inactivation generating the propagated cardiac action potential. Experimental models with specific ion channel genetic modifications have helped clarify...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12721
更新日期:2017-12-01 00:00:00
abstract::1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1440-1681.1997.tb01204.x
更新日期:1997-05-01 00:00:00
abstract::1. Kynurenine aminotransferase catalyzes the conversion of kynurenine to kynurenic acid, an endogenous antagonist of excitatory amino acid receptors. The kynurenic acid content and kynurenine aminotransferase activity was measured in micro-dissected regions of spontaneously hypertensive rats (SHR) and their normotensi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02460.x
更新日期:1994-11-01 00:00:00
abstract::1. Stretch-induced muscle injury results in the damage that causes reduced force and increased membrane permeability. This muscle damage is caused, in part, by ionic entry through stretch-activated channels and blocking these channels with Gd3+ or streptomycin reduces the force deficit associated with damage. 2. Dystr...
journal_title:Clinical and experimental pharmacology & physiology
pub_type:
doi:10.1111/j.1440-1681.2004.04027.x
更新日期:2004-08-01 00:00:00
abstract::This study explored the effects and mechanisms of dopamine D1 receptors (DR1) activation on the apoptosis of osteosarcoma cells (OS732).The DR1 agonist SKF-38393 decreased the viability of OS732 cells and increased their rate of apoptosis, whereas the DR1 antagonist SCH-23390 abolished the effects of SKF-38393. In OS7...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 信件
doi:10.1111/1440-1681.12814
更新日期:2017-11-01 00:00:00
abstract::1. The effects of left ventricular repair (LVR) surgery for ischaemic or dilated cardiomyopathy are not fully understood. The development of a proper animal model will help to resolve this issue. 2. The ischaemic cardiomyopathy (ICM) model used was as follows. Twenty-six rats developed ICM with a large akinetic left v...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2002.03708.x
更新日期:2002-08-01 00:00:00
abstract::This paper attempts to provide a short review of the evidence for: 1. Increased platelet production of thromboxane A2 and reduced vascular production of prostacyclin in the human and also animal models of diabetes. 2. Reduced depressor responsiveness to arachidonic acid of anaesthetized alloxan- and streptozotocin-ind...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1992.tb00391.x
更新日期:1992-01-01 00:00:00
abstract::1. Hypertension plays a critical role in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD), but it has also been postulated that antihypertensive drugs that block the renin-angiotensin system (RAS) show class-specific renoprotective actions beyond their blood pressure (BP)-lowering effe...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2010.05453.x
更新日期:2010-12-01 00:00:00
abstract::1. The intravenous administration of nicergoline (5 mg) was followed by a rapid and sustained lowering of blood pressure; less rapid effects were bradycardia and an elevation of cardiac output. These delayed effects are consistent with an indirect action on the alpha-adrenoreceptors of the central nervous system. 2. F...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1980.tb00051.x
更新日期:1980-03-01 00:00:00
abstract::Chronic low back pain (LBP) has high prevalence in the adult population which is associated with enormous disability. Hence, our aim was to further characterise our LBP rat model by using immunohistological and immunohistochemical methods at an advanced stage (day 49) of the model. Male Sprague-Dawley rats were anaest...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13402
更新日期:2020-09-05 00:00:00
abstract::1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16-18 g/day) and after 7 ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1992.tb00444.x
更新日期:1992-04-01 00:00:00
abstract::Sixteen stable asthmatics had the protective effects of inhaled fenoterol (200 micrograms) and inhaled ipratropium bromide (60 micrograms) against standardized histamine inhalation tests at 1 h examined in a randomized double blind fashion. There was no significant difference in the baseline forced expired volume in 1...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1440-1681.1987.tb00961.x
更新日期:1987-02-01 00:00:00
abstract::1. The effects of the Class I anti-arrhythmic drugs quinidine, procainamide, lidocaine, phenytoin and tocainide on mitochondrial lactate dehydrogenase activity were compared in guinea-pig heart preparations. 2. All the tested drugs inhibited the enzyme activity in a concentration-dependent fashion, exhibiting varying ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01671.x
更新日期:1993-04-01 00:00:00
abstract::Transthyretin (TTR) is a binding protein for the thyroid hormone thyroxine (T4 ), retinol and β-amyloid peptide. TTR aids the transfer of T4 from the blood to the cerebrospinal fluid (CSF), but also prevents T4 loss from the blood-CSF barrier. It is, however, unclear whether TTR affects the clearance of β-amyloid from...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12598
更新日期:2016-09-01 00:00:00
abstract::1. Over the past 50 years considerable evidence has been reported suggesting that endogenous opioids participate in the control of renal function. 2. Exogenous administration of opioids produces profound changes in the renal excretion of water and sodium. 3. Opioids produce changes in urine output and urine sodium exc...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1995.tb02324.x
更新日期:1995-12-01 00:00:00
abstract::1. Within the lung, endothelin (ET)-1 is synthesized and released by airway epithelial and vascular endothelial cells, as well as by inflammatory cells, such as macrophages. Following release, ET-1 can modulate the activities of a wide range of different cell types within the lung through the stimulation of specific e...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.1999.03010.x
更新日期:1999-02-01 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. Renomedullary interstitial cells (RMIC), abundant throughout the medulla of the kidney, have been demonstrated to have binding sites for many vasoactive peptides, including atrial natriuretic peptide, endothelin, angiotensin II and bradykinin (BK). These observations would support the hypothesis that interactions b...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.1999.02981.x
更新日期:1999-01-01 00:00:00
abstract::1. The present experiments were performed in order to study the role of the sarcoplasmic reticulum (SR) in the altered action potential and contraction of ventricular myocardium obtained from myopathic Syrian hamster and explanted human hearts (n = 8). The hamsters included age-matched healthy hamsters (F1B; n = 18), ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03820.x
更新日期:2003-04-01 00:00:00
abstract::1. This paper reports on the in vitro and in vivo characteristics of a non-peptide vasopressin V1 receptor antagonist 1-(1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl)-3,4-dihydro-2( 1H)- quinolinone (OPC-21268). 2. OPC-21268 caused a concentration-dependent displacement of the selective V1 receptor antagonist radio...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01713.x
更新日期:1993-05-01 00:00:00
abstract::1. The present study investigates the contribution of the sympathetic and vagal parasympathetic systems to the tachycardic response of long-lasting (40 min) conditioned fear responses to context. 2. The conditioned fear response evoked by re-exposure to a footshock chamber was tested 10 min after intravenous injection...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04519.x
更新日期:2006-12-01 00:00:00
abstract::KISS1 and KISS1R, a novel pair of metastasis suppressors, are likely to be associated with the prognosis of colorectal cancer (CRC). Here, a meta-analysis was performed to study the role of KISS1 and KISS1R in CRC. Heterogeneity, stability and publication bias were all estimated. Six publications describing a total of...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,meta分析
doi:10.1111/1440-1681.13093
更新日期:2019-07-01 00:00:00
abstract::1. Nineteen-day old rats were fed an essential fatty acid deficient diet for 37 weeks, thereby making them essential fatty acid deficient for at least 24 weeks. The weights of their brains were 33% less than those of rats on control diets. 2. When the deficient rats were rehabilitated for ten weeks on a diet containin...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1979.tb00022.x
更新日期:1979-07-01 00:00:00