Abstract：
:During recent years, small conductance Ca-activated K (SK) channels have been reported to play a role in cardiac electrophysiology. SK channels seem to be expressed in atria and ventricles, but from a functional perspective, atrial activity is predominant. A general notion seems to be that cardiac SK channels are predominantly coming into play during arrhythmogenic events where intracellular concentration of Ca is increased. During ventricular fibrillation (VF), a surge of [Ca]i has the potential to bind to and open SK channels. To obtain mechanistic insight into possible roles of SK channels during VF, we conducted experiments with an SK channel pore blocker (ICA) and a negatively allosteric modulator (NS8395) in a Langendorff-perfused heart model. Both compounds increased the action potential duration, effective refractory period, and Wenckebach cycle length to comparable extents. Despite these similarities, the SK channel modulator was found to revert and prevent VF more efficiently than the SK channel pore blocker. In conclusion, either negative allosteric modulation of the SK channel with NS8593 is more favorable than pure channel block with ICA or the 2 compounds have different selectivity profiles that makes NS8593 more antiarrhythmic than ICA in a setting of VF.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Diness JG,Kirchhoff JE,Sheykhzade M,Jespersen T,Grunnet Mdoi
10.1097/FJC.0000000000000278subject
Has Abstractpub_date
2015-09-01 00:00:00pages
294-9issue
3eissn
0160-2446issn
1533-4023journal_volume
66pub_type
杂志文章abstract：:Hibernating myocardium is characterized by chronic reduction of myocardial blood flow due to obstructive coronary artery disease, causing reversible left ventricular dysfunction and flow-metabolism mismatch. The condition is unstable and increasing demand may lead to further left ventricular dysfunction or necrosis ca...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/00005344-199906003-00002
更新日期：1999-06-01 00:00:00
abstract：:Twenty-four-hour urinary sodium excretion and plasma renin activity were monitored in 36 patients receiving bendrofluazide as sole antihypertensive therapy. There was no increase in urinary sodium output compared with pretreatment values during a 2-year period, and there is therefore no evidence that an increase in sa...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198400061-00039
更新日期：1984-01-01 00:00:00
abstract：:Acute effects of piretanide, a loop diuretic, on blood pressure (BP) and urinary output as well as long-term effects on serum electrolytes were compared in conscious spontaneously hypertensive rats (SHR) to that of hydrochlorothiazide (HCT) both given alone and in combination with the converting enzyme (CE) inhibitor ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198706107-00030
更新日期：1987-01-01 00:00:00
abstract：:We examined the actions of the isopropyl ester of palmitoyl carnitine (P1Pi), a novel vasodilator compound, on coronary constriction mediated by the calcium channel activator BAY K 8644 and positive inotropic responses mediated by norepinephrine (NE) and low sodium perfusion in perfused rat hearts. Langendorff-perfuse...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199506000-00003
更新日期：1995-06-01 00:00:00
abstract：:The acute effects of doxorubicin on coronary perfusion and left ventricular pressures and intracellular phosphate metabolite levels, the latter obtained by 31P nuclear magnetic resonance, were measured simultaneously in isolated, isovolumic rat hearts (Langendorf preparation) perfused at constant flow. Nineteen experi...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:This study examined whether the adenosine potentiator, 5-aminoimidazole-4-carboxamide riboside (AICAr), could limit tissue necrosis during acute myocardial infarction in rabbit hearts with minimal coronary collateral flow. Forty-four rabbits underwent 45 min of ischemia with or without coronary reperfusion for 180 min...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199201000-00010
更新日期：1992-01-01 00:00:00
abstract：:The structure-activity relationships of phosphoramidon analogues for inhibition of endothelin-converting enzyme (ECE), neutral endopeptidase 24.11 (NEP), and angiotensin-converting enzyme (ACE) were compared. Phosphoramidon inhibited ECE, NEP, and ACE activities with IC50 values of 3.5, 0.034, and 78 microM, respectiv...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:We investigated the interaction between nitroxy groups and angiotensin-converting enzyme (ACE) inhibitors to assess the role of sulfhydryl groups and adenosine triphosphate (ATP)-sensitive potassium channels in vasodilation of human coronary resistance vessels in vitro. Coronary resistance vessels were resected from t...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章
doi：10.1097/00005344-200010000-00001
更新日期：2000-10-01 00:00:00
abstract：:Endothelin-1 (ET-1) is an endothelium-derived peptide with powerful vasoconstrictor and mitogenic properties. A pathophysiologic role for ET-1 has been suggested, because increased plasma and tissue levels of this peptide have been described in a number of disease states, including atherosclerosis. Immunocytochemistry...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:We examined a relation between cyclic guanosine monophosphate (cGMP) production in thoracic aorta, as an indicator probably reflecting the vascular response, and the vascular as well as plasma levels of nicorandil administered orally to rats. Nicorandil (3 mg/kg) given orally was rapidly absorbed, reaching the maximal...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199804000-00019
更新日期：1998-04-01 00:00:00
abstract：:LC3B is a marker of autophagic activity, and growing evidence supports its importance in myocardial hypertrophy. Thus, regulating LC3B expression may provide an important avenue to inhibit autophagy and protect against or inhibit pathological myocardial hypertrophy. To address this question, we investigated the effect...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0000000000000306
更新日期：2015-12-01 00:00:00
abstract：:The relation between insulin resistance/ hyperinsulinemia and cardiovascular disease may be related to one of the cardiovascular effects of insulin. In acute experiments in humans, systemic euglycemic hyperinsulinemia induced vasodilation in skeletal muscle. Furthermore, the sympathetic nervous system is activated, al...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章
doi：10.1097/00005344-199608000-00010
更新日期：1996-08-01 00:00:00
abstract：:Kinins elicit prostaglandin and inositol phosphate production in 3T3 fibroblasts through stimulation of B2 receptors. Prostaglandin synthesis is maximum by 5 min, whereas inositol phosphate production continues for longer than 30 min. Prostaglandin synthesis is stimulated by phospholipase A2, which releases arachidona...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:Apoptosis, a genetically controlled programmed cell death, has been found to play a role in ischemic reperfusion injury in several animal species including rats and rabbits. To examine whether this also is true for other animals, a surgically relevant model was established using an isolated in situ swine heart. Hearts...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200011000-00009
更新日期：2000-11-01 00:00:00
abstract：:Pro-arrhythmia by noncardiac drugs has become an important safety concern in the pharmaceutical industry. The most common underlying mechanism for induction of arrhythmias by noncardiac drugs is off-target block of the native cardiac repolarizing current, I Kr. The pore-forming subunit of I Kr is encoded by the human ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e31817532ee
更新日期：2008-06-01 00:00:00
abstract：:Forskolin exerts concentration-dependent positive inotropic effects in guinea pig isolated papillary muscles; resting potential, overshoot, and upstroke velocity remain unchanged. It markedly potentiates Ca2+-mediated action potentials elicited in partially depolarized myocardial fibers (increases in upstroke velocity...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:Acute bromocriptine administration reduced sitting and standing blood pressure and produced severe orthostatic hypotension in 12 normal subjects. Concomitantly, there was an increase in venous distensibility and basal blood flow, and a decrease in peripheral vascular resistance, as determined by forearm plethysmograph...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198407000-00005
更新日期：1984-07-01 00:00:00
abstract：:Pentoxifylline possesses vasodilator properties, but little information is available on the mechanism of action explaining this vasodilator effect. The present experiments were designed to determine the effects of the compound on vascular smooth muscle, endothelium, and adrenergic nerves in rings of isolated canine bl...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198912000-00017
更新日期：1989-12-01 00:00:00
abstract：:To evaluate the role of intracellular calcium and particularly Ca2+-uptake in the initiation of lymphocyte mitogenesis, the effect of mibefradil, which blocks both L- and T-type calcium channels with a more selective blockade of T-type channels, on the proliferation of human peripheral blood mononuclear cells (PBMCs) ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199904000-00012
更新日期：1999-04-01 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：:The "Oxford" system for continuous monitoring of the ambulatory blood pressure was used to assess the changes in blood pressure following therapy with the calcium ion antagonists verapamil and nifedipine in two separate groups of patients. In the first group 16 patients were studied on both no therapy and following a ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-01-01 00:00:00
abstract：:We have previously demonstrated that cocaine induces apoptosis in primary cultures of fetal rat cardiomyocytes. The current study was designed to determine whether cocaine administered to the mother during pregnancy induced apoptosis in fetal rat heart. Pregnant rats were treated with cocaine subcutaneously (30 and 60...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200106000-00001
更新日期：2001-06-01 00:00:00
abstract：:The effects of two antihypertensive agents, nifedipine (N) and captopril (C), on left ventricular (LV) mass and volume were studied in 16 patients with essential hypertension (8 treated with N and 8 with C for 6 months) by means of a complete M-mode echocardiogram monitored by two-dimensional echocardiography. Both N ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章
doi：
更新日期：1987-01-01 00:00:00
abstract：:Regeneration of the heart after a stroke would be the best biologic response to restore its function. However, although this phenomenon occurs in primitive organisms, the regenerative potential is lost in mammals. Thus, the search for an appropriate cardiac progenitor with the potential to differentiate into a functio...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/FJC.0b013e3181d8bc6d
更新日期：2010-07-01 00:00:00
abstract：:Platelet-derived growth factor (PDGF), a potent mitogen and chemoattractant for smooth muscle cells and fibroblasts in culture, is believed to play an important role in the formation of proliferative lesions of arterio-sclerosis. PDGF appears as three different dimeric isoforms: AA, AB, and BB. These were recently fou...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：:Hypertension is a major disease in the black population of sub-Saharan Africa and the U.S. The prevalence of hypertension varies from 1-30% of the adult population. Differences in blood pressure (BP) between black and white patients have been documented. In this review, genetic, endocrine, and environmental characteri...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1990-01-01 00:00:00
abstract：:With increasing age, cardiac beta-adrenoceptor function decreases. To study possible mechanisms underlying this process, we assessed in right atrial appendages from 52 patients of different ages (group A, < 20 years, mean age 3.7 +/- 1.0 years, n = 20; group B, 20-50 years, mean age, 37.9 +/- 2.3 years, n = 9; group C...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章
doi：10.1097/00005344-199507000-00004
更新日期：1995-07-01 00:00:00
abstract：:Diabetic nephropathy is a major cause of end-stage renal failure and the mortality rate due to this disease is continuously progressing worldwide. The multifaceted signalling mechanisms have been identified to be involved in the pathogenesis of diabetic nephropathy. Despite the modern therapies like antidiabetics, ant...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/FJC.0b013e3181ad2190
更新日期：2009-08-01 00:00:00
abstract：:Diazepam (DZP) is commonly used in treatment of patients with acute ischemic syndromes to allay anxiety, but benzodiazepines reduce myocardial contractility and increase myocardial blood flow. To investigate the antiischemic effect of DZP, we studied 13 patients with a positive exercise test and angiographically docum...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1097/00005344-199407000-00010
更新日期：1994-07-01 00:00:00
abstract：:Three consecutive periods in the natural history of atherosclerosis are amenable to medical treatment. Plaque development is the main target of prevention, which also aims at slowing the progression of already existing plaques. The control of several established risk factors (high blood cholesterol, high blood pressur...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/00005344-199500252-00009
更新日期：1995-01-01 00:00:00
