Abstract:
:The signaling impact of a human beta1-adrenergic receptor (beta1 AR) polymorphism at residue 49 of the aminoterminus (Ser-to-Gly substitution) was studied by recombinantly expressing each receptor. The two receptors displayed identical agonist and antagonist binding affinities. Furthermore, basal and agonist-stimulated adenylyl cyclase activities were the same for these receptors as assessed in both cell types. Although short-term agonist exposure resulted in similar degrees of receptor internalization, long-term agonist-promoted downregulation was greater for Gly49 compared with Ser49. The Gly49 receptor underwent a 24 +/- 3% loss of receptor density after exposure to isoproterenol for 18 h, whereas Ser49 underwent no such loss. In studies in which receptor synthesis was inhibited, agonist-promoted downregulation for Gly49 was 55 +/- 3% compared with 36 +/- 5% for Ser49. In the absence of agonist, degradative turnover of each receptor was the same. Immunoblotting revealed that some of the Ser49 receptor exists as a highly N-glycosylated form (approximately 105-kD molecular mass), which is not present with Gly49. Thus the phenotype of the Gly49 polymorphic receptor is that of wild-type coupling with enhanced agonist-promoted downregulation, which is associated with altered N-glycosylation. Based on this cellular phenotype, the beta1 AR Gly49 polymorphism may impart a beneficial effect in chronic heart failure.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Rathz DA,Brown KM,Kramer LA,Liggett SBdoi
10.1097/00005344-200202000-00001subject
Has Abstractpub_date
2002-02-01 00:00:00pages
155-60issue
2eissn
0160-2446issn
1533-4023journal_volume
39pub_type
杂志文章abstract::The antihypertensive efficacy of the calcium entry blocker nitrendipine administered as monotherapy (20-80 mg; mean, 36/day) on the average for 144 days to 46 patients with essential hypertension (WHO I and II) was investigated in relation to age, pretreatment blood pressure, and plasma renin activity. In addition, we...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::Beta-adrenergic-blocking drugs (BABs) have a firm place in the therapy of cardiovascular conditions including angina and hypertension. Although all BABs are competitive inhibitors of beta-receptors, they may differ in their additional pharmacodynamics, i.e., beta1-(cardio)selectivity, partial agonistic activity (PAA),...
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::Although myocardial ischemia is associated with regional cardiac sympathetic nerve deterioration, it remains unknown whether acute hindlimb ischemia impairs muscle sympathetic nerve function. In the study presented here we implanted dialysis probes in the adductor muscle of anesthetized rabbits and measured dialysate ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200312001-00003
更新日期:2003-12-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-200310000-00002
更新日期:2003-10-01 00:00:00
abstract::In response to acetylcholine, endothelial cells were shown to release a nonprostanoid factor, called endothelium-derived relaxing factor (EDRF), which caused relaxation of vascular smooth muscle. Since this discovery in 1980, many additional agents have been shown to stimulate release of EDRF from endothelium. Biologi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1993-01-01 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::Current drug screening methods are insufficiently predictive of clinical toxicity and efficacy. Recent advances in stem cell technology have the potential to improve drug screening. For tests of cardiotoxicity and efficacy of cardioactive drugs, cardiomyocytes derived from human embryonic stem cells and/or human induc...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31821823f5
更新日期:2011-09-01 00:00:00
abstract::To evaluate the safety and pharmacologic activity of ITF 296 in humans, three groups of healthy male normotensive subjects were studied. The first two groups (six subjects each) received, in ascending order, three dose levels of ITF 296 by 30-min intravenous infusion (group I, 0.1, 0.5, 1.0 microgram/kg/min; group II,...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1995-01-01 00:00:00
abstract::The purpose of this study was to determine the receptor subtype mediating enhanced contractile responses of aortae and mesenteric arteries from diabetic rats to the alpha-adrenoceptor agonists, norepinephrine, clonidine, and methoxamine and to establish whether the enhanced responses are associated with increased rele...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199008000-00010
更新日期:1990-08-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/FJC.0b013e3181c37da4
更新日期:2010-01-01 00:00:00
abstract::The aim of this study was to investigate the effect of hypercholesterolemia on the angiotensin II-induced contractions in the isolated aorta and iliac artery of the rabbit, with respect to the role of arachidonate metabolites. Furthermore, the effect of the angiotensin-converting enzyme inhibitor ramipril was studied ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199707000-00017
更新日期:1997-07-01 00:00:00
abstract::Vasopressin is the primary physiological factor regulating renal water reabsorption in mammals. Inhibitors of vasopressin-stimulated water reabsorption have previously been used as water diuretic agents in both experimental animals and man. The present studies describe and characterize the pharmacological effects of t...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198600087-00008
更新日期:1986-01-01 00:00:00
abstract::Intravenous (i.v.) administration of bromocriptine (150 micrograms/kg) in conscious normotensive rats with chronic spinal cord transection (at T5-T7), pretreated or not with i.v. propranolol (0.5 mg/kg), induced significant decreases in mean arterial blood pressure (MAP) which were greater and longer lasting than thos...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::We compared the beta-adrenoceptor blocking actions of bupuranolol and propranolol using the response to isoprenaline of the strength of contraction of the canine blood-perfused ventricular muscle, of the rate and strength of contraction of the isolated guinea pig heart and of a guinea pig tracheal ring preparation. Th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-197903000-00004
更新日期:1979-03-01 00:00:00
abstract::To elucidate the pathophysiological role of atrial natriuretic polypeptide (ANP) in diseased hearts, ANP levels in atrial and ventricular tissues and plasma were investigated in mice with congestive heart failure after viral myocarditis. The study was performed on day 14 after encephalomyocarditis viral inoculation, w...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::In helical strips of dog cerebral, coronary, mesenteric, and renal arteries treated with ONO3708, an inhibitor of vasoconstricting prostaglandin (PG) receptors, and previously contracted with serotonin, PGF2 alpha, PGD2 and epithio-methano thromboxane A2 (sTxA2), a TxA2 analog, caused a relaxation. The cerebral arteri...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198803000-00014
更新日期:1988-03-01 00:00:00
abstract::The cardiovascular effects of intracerebroventricular (i.c.v.) administration of choline were studied in endotoxin-treated rats. Intravenous (i.v.) endotoxin (20 mg/kg) caused a moderate hypotension and tachycardia within 10 min of treatment. Choline (50, 100, and 150 microg; i.c.v.) increased blood pressure and decre...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199711000-00018
更新日期:1997-11-01 00:00:00
abstract::Peroxisome proliferator-activated receptors (PPAR) play a critical physiological role in energy homeostasis, in inflammation, and a protective role in cardiovascular function. We assessed the antioxidant effect of clofibrate-induced Peroxisome proliferator-activated receptor alpha (PPARα) stimulation on ischemic myoca...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31826216ed
更新日期:2012-10-01 00:00:00
abstract::High blood pressure (BP) is associated with increased risk of vascular disease, including myocardial infarction and stroke. Since drugs that lower BP will reduce the risk of those complications of hypertension that are due to high pressure (strokes due to small-vessel disease, including lacunar infarction and intracer...
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::Several recent studies demonstrate that T lymphocytes and monocytes enter the vessel wall during pathologic conditions and accumulate both in atherosclerotic and arteritic lesions. This brief review summarizes our phenotypic analysis of such T lymphocytes. Effects of T lymphocytes and their secretory products (lymphok...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1989-01-01 00:00:00
abstract:BACKGROUND:S-equol is known as an estrogenic substance, but its ability to restore vascular endothelial function is unknown. The aim of this study was to investigate the impact of S-equol on endothelial function and intimal thickening under isoflavone- and estrogen-deficient circumstances. METHODS:Twelve-week-old fema...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000220
更新日期:2015-05-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:
更新日期:1981-01-01 00:00:00
abstract::Our previous study found that angiotensin-converting enzyme (ACE) inhibitors and amlodipine induce NO release from coronary microvessels through a kinin-dependent mechanism. The goal of this study was to determine whether amlodipine could potentiate NO formation during ACE inhibition. Coronary microvessels were isolat...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200002000-00004
更新日期:2000-02-01 00:00:00
abstract::Endothelin-1 (ET-1) is a 21-amino-acid local and circulating factor whose plasma concentrations are increased in advanced atherosclerosis. ET-1 is cleaved from a prohormone (big ET-1) by endothelin-converting enzymes (ECEs) into the biologically active mature form which mediates vasoconstriction and cell proliferation...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199800001-00009
更新日期:1998-01-01 00:00:00
abstract::We have previously shown that amiloride suppresses the induction of sustained ventricular tachycardia both in dogs late following myocardial infarction and in patients. In those studies the only electrophysiologic correlate of amiloride's antiarrhythmic activity observed was prolongation of ventricular effective refra...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199106000-00004
更新日期:1991-06-01 00:00:00
abstract::Anesthesia inhibits arterial baroreflex functions such as baroreflex sensitivity (BRS). The main objective of the present study was to determine the time course of BRS recovery from anesthesia and to determine whether BRS recovery is synchronous with the recovery of consciousness and blood pressure (BP). Experiments w...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200401000-00001
更新日期:2004-01-01 00:00:00
abstract::We studied the hemodynamic effects of four doses of milrinone, administered by intravenous (i.v.) infusion alone and after autonomic blockade with prazosin, propranolol, atropine, and clonidine. Plasma concentrations of milrinone (50-600 ng/ml) were similar to those used for the treatment of cardiac failure and were u...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198705000-00002
更新日期:1987-05-01 00:00:00
abstract::We conducted an intracardiac study of the electrophysiologic effects and kinetics of intravenous nicardipine (N) in 16 patients with or without impaired cardiac conduction, using a randomized, double-blind, crossover design versus placebo (P). N or P were infused intravenously over 5 min: the dose of N was 9.46 +/- 3....
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199001000-00021
更新日期:1990-01-01 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::Recent studies have shown the ability of salicylic acid (SA) to trap hydroxyl radicals (OH.) generated during reperfusion in ischemic myocardium. Since OH. is implicated in the pathogenesis of reperfusion injury, we examined the effect of SA on reperfusion-induced arrhythmias and postischemic ventricular dysfunction. ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199202000-00009
更新日期:1992-02-01 00:00:00