Abstract:
:Primary pulmonary hypertension continues to be a fatal disease. We have recently demonstrated that long-term inhibition of Rho-kinase, an effector of the small GTPase Rho, is effective for the treatment of pulmonary hypertension (PH) in rats and humans. Prostacyclin has been clinically used for the treatment of PH with moderate success. However, it remains to be examined whether Rho-kinase inhibition is involved in its beneficial effects on PH. In an ELISA assay, neither prostacyclin nor its oral analogue, beraprost sodium, inhibited Rho-kinase even at higher concentrations (10(-7) to 10(-5) M, 100 to 10,000 times higher than their clinical concentrations), whereas specific Rho-kinase inhibitors, fasudil and hydroxyfasudil, markedly (approximately 95%) inhibited the Rho-kinase activity at 10(-5) M (near their clinical concentrations). Beraprost sodium did not significantly suppress serotonin-induced vascular smooth muscle cell (VSMC) contractions or Rho-kinase activity of the rat aorta without endothelium, as evaluated by the extent of phosphorylation of the ERM family, a substrate of Rho-kinase, whereas hydroxyfasudil markedly suppressed the VSMC contractions and Rho-kinase activity. These results indicate that prostacyclin lacks direct inhibitory effect on Rho-kinase and suggest that combination therapy with prostacyclin and a Rho-kinase inhibitor could exert further beneficial effects on PH.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Abe K,Morikawa K,Hizume T,Uwatoku T,Oi K,Seto M,Ikegaki I,Asano T,Kaibuchi K,Shimokawa Hdoi
10.1097/01.fjc.0000151898.65260.6asubject
Has Abstractpub_date
2005-02-01 00:00:00pages
120-4issue
2eissn
0160-2446issn
1533-4023pii
00005344-200502000-00004journal_volume
45pub_type
杂志文章abstract::Antecubital venous plasma neuropeptide Y-like immunoreactivity (NPY-LI) and catecholamines were analyzed in six healthy volunteers performing a graded bicycle exercise without medication and after acute administration of clonidine, phentolamine, and nifedipine. During the control exercise, plasma noradrenaline (NA), a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198811000-00014
更新日期:1988-01-01 00:00:00
abstract::Three agents with K(+)-channel-opening activity--nicorandil, bimakalim (EMD 52692), and EMD 56431--were tested for vasorelaxation abilities in human coronary artery and human arteria mammaria. The potency orders were bimakalim = EMD 56431 > nicorandil for relaxation in human coronary artery and bimakalim = EMD 56431 >...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199206203-00004
更新日期:1992-01-01 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::The majority of deaths attributable to hypertension are coronary artery disease (CAD) deaths and, consequently, the prevention of CAD should be the primary aim of hypertension management. Recent meta-analyses confirm the results of the individual hypertension intervention trials, which demonstrated a disappointing sho...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1991-01-01 00:00:00
abstract::Fourteen patients with mild to moderate essential hypertension were randomized, after a baseline placebo period of 4 weeks, to receive the angiotensin converting enzyme (ACE) inhibitor quinapril or a placebo. During a 12 week, double-blind phase, the dosage of quinapril was increased from 10 to 40 mg twice daily being...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198807000-00012
更新日期:1988-07-01 00:00:00
abstract::When the cervical vagus nerve is briefly stimulated, a triphasic cardiac chronotropic response ensues: the cardiac cycle length initially increases, then briefly decreases, and subsequently increases again. Verapamil, a calcium channel blocker, alters these responses to acetylcholine when the heart is in sinoatrial no...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198807000-00017
更新日期:1988-07-01 00:00:00
abstract::Serotonin (5-hydroxytryptamine, 5-HT) mediates vasoconstriction and vasodilation in normal coronary circulation of various animal species. In the presence of coronary artery disease, serotonin may inhibit coronary collateral formation and stimulate predominantly vasoconstriction. We tested the effect of ketanserin, a ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199301000-00021
更新日期:1993-01-01 00:00:00
abstract::Many radioligands used to study neurotransmitter receptors label multiple subtypes or multiple classes of receptors. Frequently, two subtypes or classes of receptors coexist in the same tissue and exhibit only slightly different affinities for a radioligand. A new analytical method has been developed to quantitate the...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::To study the effects of chronic in vivo inhibition of NO synthase on endothelium-dependent hyperpolarization, cell-membrane potential (in individual vascular smooth-muscle cells) and changes in tension (in isolated rings) were recorded from isolated canine coronary arteries and guinea-pig carotid arteries and aortas. ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199812000-00011
更新日期:1998-12-01 00:00:00
abstract::The dependency of arteriolar tone on calcium influx was studied in 11 patients with essential hypertension (EHT) and compared to 11 age-matched normotensive (NT) subjects by measuring the forearm blood flow (FAF) response to intraarterial infusion of the calcium channel blocker verapamil (Verap) and the nonspecific va...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::Heart failure is unique among the major cardiovascular disorders in that it alone is increasing in prevalence while there has been a striking decrease in other conditions. Some of this can be attributed to the aging of the U.S. and European populations. The ability to salvage patients with myocardial damage is also a ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200111002-00015
更新日期:2001-11-01 00:00:00
abstract::Coronary artery reperfusion established by thrombolytic agents early in the evolution of an acute myocardial infarction is known to result in the salvage of otherwise jeopardized heart muscle. Recently, experimental evidence has suggested that reactive products of oxygen are formed as a result of reperfusion and can i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198808000-00009
更新日期:1988-08-01 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 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. Elec...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-07-01 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::Insulin resistance is an important risk factor for the development of hypertension, atherosclerotic heart disease, left ventricular hypertrophy and dysfunction, and heart failure. It reflects a disturbance of glucose metabolism and potentially worsens metabolic efficiency of both skeletal muscle and cardiac muscle. Th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-200000004-00002
更新日期:2000-01-01 00:00:00
abstract::There is no systematic study in which the effects of vasoactive substances were investigated on pulmonary vascular resistance (PVR) in in vivo mouse by directly measuring cardiac output and the inflow and outflow pressures in the pulmonary circulation. We determined the responses of PVR, total peripheral resistance (T...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000199
更新日期:2015-04-01 00:00:00
abstract::Endothelin (ET) may play an important role in the pathogenesis of vasoconstriction and acute renal failure after aortic cross-clamping (ACC). However, the relative contribution of the ET(A) and ET(B) receptors to the physiopathology of ischemic acute renal failure is poorly understood. This study was carried out to ev...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199908000-00004
更新日期:1999-08-01 00:00:00
abstract::Chronic rapid right ventricular pacing (RRVP) at 250 beats/min produces low cardiac output (CO) heart failure, marked reduction in total vascular capacitance, and a shift in volume centrally. The effect of converting enzyme inhibition with captopril on cardiac preload was investigated in this model of heart failure. E...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199409000-00002
更新日期:1994-09-01 00:00:00
abstract::We have previously reported the production of endothelin-1 (ET-1) by the cerebral microvessel endothelia and suggested an important role of ET-1 and microvessel endothelia in the regulation of local blood flow within the brain. In the present study, radioimmunoassay of ET-1 revealed that ET-1, produced by cultured cer...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00074
更新日期:1991-01-01 00:00:00
abstract::(+/-)-Dobutamine at concentrations < or =10(-5) M did not evoke contractions of rat gastric artery segments. However, when the tissues were contracted with methoxamine, (+/-)-dobutamine evoked concentration-dependent relaxation. The relaxant responses were not significantly affected by propranolol. In the same prepara...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199911000-00015
更新日期:1999-11-01 00:00:00
abstract::We investigated the effects of a newly synthesized dihydropyridine (DHP) derivative (NZ-105) on intracellular Ca transients and contraction in ferret ventricular muscles, using the aequorin method. Low concentrations of NZ-105 (10(-9)-10(-7) M) showed no significant effects on the light signal of aequorin and tension ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 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::Vasopressin is an essential hormone involved in the maintenance of cardiovascular homeostasis. It has been in use therapeutically for many decades, with an emphasis on its vasoconstrictive and antidiuretic properties. However, this hormone has a ubiquitous influence and has specific effects on the heart. Although diff...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000092
更新日期:2014-07-01 00:00:00
abstract::Vascular endothelial cell (EC) wound healing was characterized on an EC-synthesized extracellular matrix (ECM) previously treated with enzymes and antibodies specific for ECM components. Using a computer-assisted video-microscope recording system capable of automatic EC recognition, we learned whether components of th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199322004-00005
更新日期:1993-01-01 00:00:00
abstract::The phosphodiesterase inhibitor UK 61260 exhibits positive inotropic activity in animal studies and is under clinical investigation for treatment of congestive heart failure (CHF). We examined the lusitropic and inotropic responses to UK 61260 in electrically driven (1 Hz, 37 degrees C) human auricular trabeculae (AUT...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199206000-00019
更新日期:1992-06-01 00:00:00
abstract::We examined four commercially available human cell lines for endothelin-converting-enzyme-(ECE) like activity and compared the results with primary porcine aortic endothelial cell enzymes. The cells that were investigated were 293 (transformed primary human embryonal kidney), Hep G2 (human hepatocellular carcinoma), H...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199322008-00025
更新日期:1993-01-01 00:00:00
abstract::There is increasing interest in initial therapy of hypertension with sympatholytic agents and the influence of antihypertensive therapy on cardiac and renal function. We treated 26 men with essential hypertension with either guanabenz alone (n = 14) or propranolol alone (n = 12) and assessed blood pressure and renal p...
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:1984-01-01 00:00:00
abstract::Disorders of the cardiac conduction system occur frequently and may cause life-threatening arrhythmias requiring medication or electronic pacemaker implantation. Repair or regeneration of conduction system components is currently not possible due to limited knowledge of the molecular regulation of pacemaker myocardium...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e3181e775d3
更新日期:2010-07-01 00:00:00
abstract::Endothelin (ET) receptor subtypes in human prostate with benign prostatic hyperplasia were investigated by binding and functional studies. In the displacement experiment, LU224332 [endothelin-A/-B (ET(A)/ET(B)) nonselective antagonist] competed for [125I]ET-1 binding with a monophasic curve. On the other hand, LU13525...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200036051-00074
更新日期:2000-11-01 00:00:00