Abstract:
:The propyl derivative of ajmaline, N-n-propylajamaline (prajmalium), is an antiarrhythmic compound that lacks the commonly reported negative inotropic effects of all others under clinical use. The present study was undertaken to establish and understand its effects at the cellular level in mammalian preparations. Electrical and mechanical activities were recorded from right ventricular strips and Na and L-type Ca currents (INa and ICaL, respectively) were recorded with the whole-cell patch-clamp technique in right ventricular myocytes freshly dissociated from rabbit hearts. Prajmalium decreased the maximal rate of depolarization of the action potential in a dose-dependent manner with an EC50 of 3 microM. This effect was use and frequency dependent. Action potential duration was increased by 1 microM prajamalium but decreased on applying higher concentrations. The force of contraction was slightly (15%) increased at 0.1 microM, not affected at all at 1 microM and depressed by 30% at 20 microM. In single cardiomyocytes maintained at negative holding potentials, INa was slightly depressed by prajmalium at 10 nM and reduced by 75% at 10 microM. ICaL was increased by 30 and 20% on applying prajmalium at 1 and 10 microM, respectively; on the other hand, ICaL was reduced by these two concentrations of prajmalium at less negative holding potentials. A higher prajmalium concentration (100 microM) decreased ICaL at all holding potentials studies and this effect was enhanced with depolarization. The increase in ICaL induced by prajmalium (1 microM) was also observed after ICaL had been fully beta-adrenergic and P2-purinergic stimulated by isoproterenol (1 microM) in the presence of IBMX (100 microM) and ATP (10 microM). It is concluded that prajmalium is able to increase ICaL in rabbit ventricular cells in a voltage-dependent manner, an effect that could account in part for the observed lack of negative inotropism of this antiarrhythmic in clinics.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Alvarez JL,Rubio L,Garrido G,Vassort Gsubject
Has Abstractpub_date
1992-07-01 00:00:00pages
43-9issue
1eissn
0160-2446issn
1533-4023journal_volume
20pub_type
杂志文章abstract::Bay k 8644, a new dihydropyridine calcium channel activator has been shown to have positive inotropic and vasoconstrictor properties following intravenous (i.v.) administration. In the present study, intracoronary administration of Bay k 8644 was used to isolate drug effects on regional myocardial blood flow and contr...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198611000-00019
更新日期:1986-11-01 00:00:00
abstract::The pharmacokinetics of losartan and EXP3174, an active metabolite of losartan, were evaluated in the anesthetized pig after both a single intravenous dose (3 mg/kg) and during constant intravenous infusion. The pharmacodynamic activities of losartan and EXP3174 were determined during constant intravenous infusion as ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199711000-00008
更新日期:1997-11-01 00:00:00
abstract::Sixty patients with mild to moderate essential hypertension, uncontrolled with diuretics alone, were evaluated in a double-blind randomized study that compared the effect of indoramin plus hydrochlorothiazide with that of pindolol plus hydrochlorothiazide. Following a 2-week period during which the patients were treat...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198600082-00013
更新日期:1986-01-01 00:00:00
abstract::To assess flecainide's ability to suppress ventricular fibrillation during reperfusion, we compared flecainide acetate (2 mg/kg i.v.) with saline placebo in 50 pentobarbital-anesthetized dogs undergoing proximal anterior descending coronary artery occlusion for 20 min followed by sudden release. Treatment selection wa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::Acetazolamide (ACTZ) vasodilating properties are used for the assessment of cerebral vasodilatory reserve not only in cerebral pathology investigation, but also in clinical pharmacology studies. However, the kinetics of these vasodilating properties are not clearly established; moreover, the cerebral selectivity of AC...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199511000-00022
更新日期:1995-11-01 00:00:00
abstract::The superoxide radical scavenging effects of the SH group in the captopril molecule has been proposed to be the basis of the "cadioprotective" effect of this angiotensin converting enzyme (ACE) inhibitor in animal models of myocardial injury. We determined the effects of captopril, another ACE inhibitor with an SH gro...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199011000-00023
更新日期:1990-11-01 00:00:00
abstract::Guinea pig papillary muscles were preincubated in the presence of 5 x 10(-9) mol/L unlabeled noradrenaline or adrenaline then incubated with (3H)-noradrenaline and superfused. Electrical field stimulation with 180 pulses delivered at 1 or 3 Hz was used to induce overflow of radioactivity. Comparison of the effects of ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199102000-00011
更新日期:1991-02-01 00:00:00
abstract:UNLABELLED:The role of mitochondrial transporters in the cardioprotection of rat hearts exposed to high [K+]-low [Ca2+]-cardioplegia (CPG) and ischemia and reperfusion (I/R) was studied through the mechano-energetic consequences of target drugs. The total heat rate (Ht) and the left intraventricular pressure (LVP) were...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181b04ce3
更新日期:2009-09-01 00:00:00
abstract::The major aim of treatment of arterial hypertension is to reduce the increased risks of cardio-cerebrovascular morbidity and mortality that are associated with elevated blood pressure (BP). A direct relationship can be found between the level of BP and risk, even down to what is normally considered to be the "normoten...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1987-01-01 00:00:00
abstract::The complementary antihypertensive effects of the beta-blocker/calcium antagonist combination has to be weighed against their additive and potentially detrimental negative inotropic, chronotropic, and dromotropic effects inherent in both classes of drugs. We reviewed the main adversity, particularly electrophysiologic...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198507004-00008
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND:There is increasing evidence that endogenous sex hormones regulate vascular reactivity, and testosterone may contribute to the worse prognosis for renal disease in men. Male Zucker diabetic rats exhibit improved renal hemodynamic responses after castration. It is, however, unclear whether endogenous testoste...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000246941.84607.11
更新日期:2006-11-01 00:00:00
abstract::We used isolated superior mesenteric arteries (SMAs) from hemorrhagic-shock rats and hypoxia-treated vascular smooth muscle cells (VSMCs; mimicking the shock state) to observe the effects of platelet-derived growth factor (PDGF; Rac1 stimulator) and NSC23766 (Rac1 antagonist) on vascular reactivity and the relationshi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318215e21d
更新日期:2011-06-01 00:00:00
abstract::Aldosterone is increased in diabetes and contributes to the development of diabetic nephropathy. The authors hypothesized that reduction in aldosterone production in diabetes by amlodipine or aliskiren improves diabetic kidney disease by attenuating renal oxidative stress and fibrosis. Normoglycemic and streptozotocin...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318274d2ef
更新日期:2013-01-01 00:00:00
abstract::In the absence of formal clinical trials, the efficacy of thiazide diuretics in patients with renal impairment remains in doubt. Our study was therefore designed to evaluate the separate and combined effects of single and multiple doses of hydrochlorothiazide (HCTZ) and furosemide (FU) on the glomerular filtration rat...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199509000-00008
更新日期:1995-09-01 00:00:00
abstract::Nitric oxide (NO) is a potent inhibitor of platelet aggregation. However, the benefits of NO-based therapies can be confounded by concomitant hypotension. Monophosphoryl lipid A (MLA) is a nontoxic derivative of endotoxin that purportedly increases nitric oxide synthase (NOS) activity and, presumably, NO production, y...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200003000-00004
更新日期:2000-03-01 00:00:00
abstract::The purpose of this study was to examine whether tetrahydrobiopterin (BH4), one of the cofactors of nitric oxide (NO) synthase, attenuates endothelial cell death induced by 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1), which is known to produce both superoxide and NO. Endothelial cell death was assessed by the rel...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199902000-00018
更新日期:1999-02-01 00:00:00
abstract::The complex formed between endothelin (ET) and its binding protein was adequately stable to be separated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) at low temperature. Cross-linking was not necessary. This simple method was applied for both qualitative (determination of molecular weight ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00028
更新日期:1991-01-01 00:00:00
abstract::Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea syndrome (OSAS), has been reported to play a key role in the development of OSAS-associated cardiovascular diseases including cardiac remodeling. RhoA/Rho-kinase (ROCK) pathway has also been implicated in myocardial remodeling, but the exact m...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000496
更新日期:2017-08-01 00:00:00
abstract::Angiotensin II receptor blockers (ARBs) are used for the treatment of patients with heart failure and hypertension. Yet their safety has been questioned by some who observed delayed cardiac healing and scar thinning after myocardial infarction (MI). To clarify potential efficacy and safety of ARBs, we administered Azi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318288a6d7
更新日期:2013-05-01 00:00:00
abstract::The terminal phases of volume-overload heart failure are characterised by eccentric ventricular hypertrophy. Relatively little attention has been directed to exploring the mechanisms involved in this development. The increase in diastolic wall stress leads to replication of the sarcomeres in series. The hypertrophied ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1987-01-01 00:00:00
abstract::The effects of angiotensin-converting enzyme inhibitor captopril on infarct size and cardiovascular hemodynamics were studied in 35 conscious dogs subjected to 24 h of coronary occlusion. Following occlusion of the left anterior descending coronary artery, 10 dogs were infused with captopril 0.25 mg/kg/h i.v. (group 1...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract::To assess efficacy and side effects during chronic oral therapy, we studied the effect of ketanserin (Kn) in 17 hypertensive patients for a period up to 1 year. Ketanserin controlled blood pressure satisfactorily in 25%, in part in 50% and had little or no effect in 25%. Reduction in diastolic pressure equalled that i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198500077-00043
更新日期:1985-01-01 00:00:00
abstract::Irisin, a muscle-origin protein derived from the extracellular domain of the fibronectin domain-containing 5 protein (FNDC5), has been shown to modulate mitochondria welfare through paracrine action. Here, we test the hypothesis that irisin contributes to cardioprotection after myocardial infarction by preserving mito...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000608
更新日期:2018-12-01 00:00:00
abstract::Ca sensitivity and sensitivity to diltiazem were studied in two strains of genetically hypertensive rat [spontaneously hypertensive rats (SHRs) and genetically hypertensive (GH) rats] and their normotensive control strains [Wistar-Kyoto (WKY) and normal Wistar (N) rats] at two ages before and after establishment of si...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
abstract::As a receptor for transforming growth factor-β, nodal and activin, activin receptor-like kinase 7 (ALK7) previously acts as a suppressor of tumorigenesis and metastasis, which has emerged to play a key role in cardiovascular diseases. However, the potential effect and molecular mechanism of ALK7 on vascular smooth mus...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000857
更新日期:2020-08-01 00:00:00
abstract::Previous studies have suggested that prazosin is a selective post-synaptic alpha-receptor blocker. It has also been suggested that it may have greater blocking actions on arterioles than on venous beds. These aspects have been investigated in cats anesthetized with pentobarbital. Prazosin had no effect on conductance ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198109000-00015
更新日期:1981-09-01 00:00:00
abstract::To assess the role of angiotensin II (AII) in development of myocardial injury during ischemia and reperfusion, the effects of short-term treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril were compared with the effects of short-term treatment with L-158,338, an AII antagonist, in isolated wor...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199410000-00008
更新日期:1994-10-01 00:00:00
abstract::We investigated the effects of a class I antiarrhythmic drug, cibenzoline, on human atrial muscle in vivo. Electrophysiologic measurements were performed in 44 patients (mean age 49 +/- 15 years), before and after an intravenous infusion of cibenzoline 1.4 mg/kg in 5 min. Extrastimuli at a basic cycle length (BCL) of ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-199608000-00020
更新日期:1996-08-01 00:00:00
abstract::The pharmacologic profile of SK-1080, a nonpeptide AT1-selective angiotensin-receptor antagonist, was investigated by receptor-binding studies, functional in vitro assays with rabbit and rat aorta, and in vivo experiments in pithed rats. SK-1080 inhibited the specific binding of [125I]-[Sar1, Ile8]-angiotensin II to h...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199903000-00004
更新日期:1999-03-01 00:00:00
abstract::Coronary arteries from animals on normal diets (ND) exhibit well-maintained responses to dilators under ischemic conditions. The reported altered metabolic requirements and K+-currents in blood vessels from hypercholesterolemic animals fed high-fat diets (HF) led us to hypothesize that under metabolically depressed co...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200404000-00004
更新日期:2004-04-01 00:00:00