Abstract:
:[3H]lacidipine binding to its receptor was characterized to explain its slow onset and long duration of antihypertensive activity. Binding parameters were studied in guinea pig myocardial and cerebral membrane preparations and compared with another dihydropyridine (DHP) calcium antagonist, isradipine. Lacidipine binds competitively to the DHP calcium antagonist receptor of the L-type calcium channel. The binding is allosterically modulated by verapamil and D-cis diltiazem and activated/inhibited by divalent cations. Association and dissociation kinetics of the binding of lacidipine to the receptor were significantly slower than those of isradipine. In addition, the Bmax of lacidipine binding in guinea pig heart microsomes was significantly higher than those of other dihydropyridine calcium antagonist. The results indicate that the slow onset and long duration of action of lacidipine can be explained principally on the basis of the binding characteristics. Although no biphasic receptor binding kinetics could be detected, a fast equilibrium between the receptor and a second compartment, due to the high lipophilicity of lacidipine, cannot be excluded.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Graziani F,Ratti E,van Amsterdam FTdoi
10.1097/00005344-199602000-00017subject
Has Abstractpub_date
1996-02-01 00:00:00pages
290-6issue
2eissn
0160-2446issn
1533-4023journal_volume
27pub_type
杂志文章abstract::Acute ischemic left ventricular failure was induced in dogs by coronary embolization with plastic microspheres, resulting in reduced cardiac output (CO), increased left ventricular end-diastolic pressure (LVEDP), pulmonary capillary pressure (PCP), and total peripheral resistance (TPR). Intravenous (i.v.) administrati...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198907000-00018
更新日期:1989-07-01 00:00:00
abstract::Heart failure after myocardial infarction (MI) is associated with endothelial dysfunction. There is conflicting evidence on the exact nature of this endothelial dysfunction and how endothelium-dependent vasodilation is affected by angiotensin-converting enzyme inhibitor (ACE-I) therapy. Furthermore, consequences of ac...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000187175.05780.e2
更新日期:2005-12-01 00:00:00
abstract::The disposition of amlodipine, a new calcium-channel blocker with a slow onset and long duration of action, has been investigated in humans and in the animal species used in the evaluation of drug efficacy and safety. Pharmacokinetic studies were conducted with nonlabeled drug using specific high-pressure liquid chrom...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198812007-00012
更新日期:1988-01-01 00:00:00
abstract::In isolated rat tail arteries perfused with Krebs-Henseleit solution, ouabain, in concentrations of less than 10(-5) M, caused a concentration-dependent, noncompetitive inhibition of the vasoconstrictor response to phenylephrine. Concentrations of 10(-8) and 10(-6) M caused 30 and 61% inhibition, respectively. The inh...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198507000-00013
更新日期:1985-07-01 00:00:00
abstract::Several 3,5-pyridinedicarboxylic acid [4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-] esters, which are analogs to felodipine, were synthesized and tested for peroral activity and vascular selectivity. Structure-activity relationships demonstrate that felodipine has biological properties (selectivity and oral activ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198710001-00011
更新日期:1987-01-01 00:00:00
abstract::Several mechanisms of action for Ca2+ antagonists are possible at the vascular muscle cell membrane and at subsequent steps. In rat caudal artery, nitrendipine hyperpolarizes the resting vascular muscle cell, an action different from that of verapamil. Hyperpolarization might be expected to explain the relaxant action...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-01-01 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::The hemodynamic effects of tetramethylpyrazine were examined in 27 anesthetized open chest dogs with electromagnetic flowmeter probes on the left circumflex coronary artery and ascending aorta. Tetramethylpyrazine, 2-15 mg/kg i.v., caused prominent systemic and coronary vasodilation, with a maximum reduction of mean a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198509000-00005
更新日期:1985-09-01 00:00:00
abstract::A plethora of studies have demonstrated that cardiomyopathy represents a serious source of morbidity and mortality in patients with diabetes. Yet, the underlying mechanisms of diabetic cardiomyopathy are still poorly understood. Of interest, cytochrome P450 2J (CYP2J) and soluble epoxide hydrolase (sEH) are known to c...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000707
更新日期:2019-09-01 00:00:00
abstract::Intracellular [Ca2+]i overloading in cardiomyocytes is a fundamental pathogenic event associated with chronic aldosterone/salt treatment (ALDOST) and accounts for an induction of oxidative stress that leads to necrotic cell death and consequent myocardial scarring. This prooxidant response to Ca2+ overloading in cardi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181cf0090
更新日期:2010-03-01 00:00:00
abstract::Atherosclerosis is a complex vascular disease initiated by abnormal accumulation of plasma lipoproteins in the subendothelial space. Elevated levels of plasma triglycerides (TG) and low-density lipoprotein (LDL)-cholesterol as well as low concentrations of high-density lipoprotein (HDL) play a causal role in the devel...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000162764.12309.25
更新日期:2005-07-01 00:00:00
abstract::Left ventricular (LV) function and end-diastolic dimensions were determined during antegrade and retrograde perfusions, respectively. Isolated hearts from spontaneously hypertensive rats (SHRs) and renal hypertensive rats and SHRs to which either feldopine, nifedipine, alpha-methyldopa, or a combination of felodipine ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::Endothelium-derived relaxing factors (EDRFs) and prostacyclin (PGI2) released from endothelial cells are potent vasodilators; endothelin-1 and thromboxane A2 may be their physiological antagonists. Interactions between these vasodilators and vasoconstrictors were studied in isolated intramyocardial porcine coronary ar...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199107000-00016
更新日期:1991-07-01 00:00:00
abstract::Endothelial cells can release both relaxing and contracting factors. Since the release of endothelium-dependent relaxing factor is prevented by incubation in Ca2+-free solution and can be triggered by the Ca2+ ionophore A 23187, it must require an increase in cytoplasmic Ca2+ concentration in the endothelial cells. Ca...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198812006-00007
更新日期:1988-01-01 00:00:00
abstract::The actions of SK&F 94120, a selective phosphodiesterase (PDE III) inhibitor, have been characterised on human ventricular myocardium obtained from heart failure patients. Some actions have been compared directly with those of the drug on guinea pig and cat ventricular myocardium. SK&F 94120 caused positive inotropic ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198706000-00013
更新日期:1987-06-01 00:00:00
abstract::Late sodium channel current (late INa) is considered to be an antiarrhythmic target. The prime antiarrhythmic mechanisms of late INa inhibition have been suggested to be (1) suppression of intracellular calcium [Cai]-mediated rhythmic activity (through reduction in Cai secondary to the decrease in intracellular sodium...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000510
更新日期:2017-09-01 00:00:00
abstract::It has been proposed that cholinergic agonists inhibit the sinoatrial node discharge by shifting the activation range of the hyperpolarization-activated inward current If to more negative values or by increasing potassium conductance. In the former instance, cesium will potentiate the cholinergic inhibition by blockin...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200102000-00005
更新日期:2001-02-01 00:00:00
abstract::Depression of myocardial contractility by muscarinic agonists is dependent on underlying beta-adrenergic tone. The negative inotropic effect of muscarinic agonists is enhanced by previous beta-adrenergic stimulation, an action that has been termed accentuated antagonism. We wished to determine whether accentuated anta...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199512000-00002
更新日期:1995-12-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature characterized by elevated pulmonary artery pressure. Currently, there is no cure for this disease, and treatment is palliative. PAH therapies target 3 main pathways: prostacyclin, endothelin, and nitric oxide. The 3 distinct th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e3181f89bdb
更新日期:2010-12-01 00:00:00
abstract::Alpha 2-adrenoceptor agonists are effective antihypertensive drugs that may provide particular advantages in the treatment of many types of patients. Of those now available, guanabenz has been shown to lower serum cholesterol concentration and not to cause sodium and water retention, offering additional protection aga...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::The effects of nicorandil and other antianginal drugs on the pH of ischemic myocardium were examined in dogs anesthetized with pentobarbital. The myocardial pH was measured with a micro glass pH electrode placed in the inner layers of the area of myocardium perfused by the left anterior descending coronary artery (LAD...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::Endothelins (ETs) are a family of peptide hormones that act on G protein-coupled ET(A) and ET(B) receptors. ETs exert inotropic and chronotropic actions in the heart. Myocardial ischemia is associated with increased plasma levels of ET and cell swelling. We examined the effect of ETs on dog atrial swelling-induced chl...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200005000-00014
更新日期:2000-05-01 00:00:00
abstract::The acute effects of daunomycin on the mechanical and energetic outputs of rabbit papillary muscles have been examined at 27 degrees C using a myothermic technique. Contrary to expectations, daunomycin, in concentrations ranging from 10 to 160 micrograms/ml, acted as a positive inotropic agent in terms of peak stress ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198505000-00023
更新日期:1985-05-01 00:00:00
abstract::Cardiac hypertrophy occurs in response to increased workload, such as hypertension or valvular heart disease. Oxidative stress has been implicated in cardiac hypertrophy and in its transition to heart failure. This study was taken up with the objective to evaluate the role of oxidative stress in cardiomyoblast hypertr...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3182756ad3
更新日期:2013-01-01 00:00:00
abstract::The acute phase of myocardial infarction promotes an inflammatory response that stimulates inducible nitric oxide synthase (iNOS). We investigated the iNOS role on the rat tail vascular bed reactivity 3 days after myocardial infarction. Vasodilator and vasoconstrictor responses were determined in isolated caudal vascu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000156822.58081.be
更新日期:2005-04-01 00:00:00
abstract::The purpose of the two double-blind studies summarized in this article was to compare the antianginal and anti-ischemic effects of nicorandil with those of two different nitrate preparations. A total of 129 patients with stable New York Heart Association functional class II or III coronary heart disease were enrolled ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1992-01-01 00:00:00
abstract::A mathematical model has been developed that relates wall tension in resistance vessels to changes in both distending pressure and flow; the effect of alterations in wall: lumen ratio is taken into account. The model indicates that increased autoregulatory activity in the forearm circulation of patients with primary h...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198812006-00016
更新日期:1988-01-01 00:00:00
abstract::Sinoaortic deafferentation (SAD) is characterized by arterial pressure lability, without sustained hypertension. Although SAD rats did not become hypertensive, their isolated aortas exhibit RCs. We have investigated whether these RCs are influenced by endothelium. Aortic rings were placed in an organ chamber, and the ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31813c112f
更新日期:2007-11-01 00:00:00
abstract::Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, which is identified as an endogenous ligand for GH secretagogues receptor. Although both ghrelin and its specific receptor are expressed in blood vessels, the cardiovascular effects of ghrelin remain unknown. To clarify whether ghreli...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200206000-00001
更新日期:2002-06-01 00:00:00
abstract::We have developed three radioimmunoassays (RIAs) of varying specificities toward the endothelin (ET) isoforms. The assays are called the endothelin-1,2[125I] assay system (RPA535), the endothelin 1-21 Specific [125I] assay system (RPA555), and the endothelin-1,2 high-sensitivity [125I] assay system (RPA545). We have f...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00121
更新日期:1991-01-01 00:00:00