Abstract:
:During ischemia-reperfusion an imbalance between endothelin (ET) and nitric oxide (NO) can be responsible for microcirculatory disturbances. The aim of this study was to restore the ET/NO balance to reduce the ischemia-reperfusion injury. Hepatic ischemia was induced for 30 min in 56 Wistar rats. Sham operation, ischemia and treatment groups with the ET receptor antagonist (ERA) bosentan (1 mg/kg body weight i.v.) and the NO donor L-arginine (400 mg/kg body weight i.v.) were performed. For evaluation of hepatic microcirculation in vivo microscopy was carried out 30-90 min after reperfusion. Local hepatic tissue PO2, laser Doppler flow and aspartate aminotransferase/alanine aminotransferase (AST/ALT) levels were measured. Increased ET caused sinusoidal constriction after reperfusion to 76% of the sham group (p < 0.05), leading to significant decrease in perfusion rate (82%), liver tissue PO2 (6.9 mmHg) and erythrocyte flux (45.2% of sham group). Hepatocellular damage could be detected 6 h after reperfusion by AST/ALT increase (p < 0.05). Sinusoidal diameters were maintained at baseline in the ERA (98%) and NO (102%) groups (p < 0.05). Increased percentage of leukocytes sticking in sinusoids (144%) and venules (435%) was reduced by therapy to 110/253% (ERA) and 111/324% (NO), respectively (p < 0.05). Perfusion rate was increased to 93 and 94% (p < 0.05 vs ischemia). Local hepatic tissue PO2 was improved 30 min after reperfusion in the ERA (11.0 mmHg) as well as in the NO group (11.5 mmHg; p < 0.05 vs ischemia). Measurement with a laser Doppler flow meter revealed significant improved erythrocyte flux in both therapy groups (p < 0.05 vs ischemia). Also, the post-ischemic AST/ALT increase was reduced by therapy. In conclusion, ET evokes strong constriction of post-ischemic sinusoids, leading to microcirculatory disturbances. The maintenance of the ET/NO balance by blocking ET receptors, or providing an NO donor, protects liver microcirculation and reduces hepatic ischemia-reperfusion injury.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Uhlmann D,Uhlmann S,Spiegel HUdoi
10.1097/00005344-200036051-00064subject
Has Abstractpub_date
2000-11-01 00:00:00pages
S212-4issue
5 Suppl 1eissn
0160-2446issn
1533-4023journal_volume
36pub_type
杂志文章abstract::An open randomized hospital study conducted in 169 centers in France compared the blood pressure response to the first 36 h of treatment with perindopril (PER), 2 mg once daily, with that to captopril (CAP), 6.25 mg t.i.d., in 725 patients (mean age, 70 years; men, 67%) with echocardiographic left ventricular systolic...
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:10.1097/00005344-199906000-00017
更新日期:1999-06-01 00:00:00
abstract::N-[3,5-Dichlorophenyl] 4-[4-hydroxy-2-methoxy-phenyl] piperazine carboxamidine dihydrochloride (RS-87337) is a chemically novel antiarrhythmic agent with an electrophysiologic profile characteristic of both class III and class Ia compounds as defined by Vaughan-Williams and Campbell. In isolated superfused guinea pig ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198908000-00002
更新日期:1989-08-01 00:00:00
abstract::Both population (mass) strategies and targeted strategies for the management of high blood pressure are necessary. However, it has yet to be proven that reducing blood pressure by lifestyle changes in the population will confer the same cardiovascular benefit that results from lowering blood pressure by drugs. It is i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199627003-00008
更新日期:1996-01-01 00:00:00
abstract::In this retrospective study, a group of 435 patients provided meaningful analyses of blood pressure and dosage data for treatment periods of up to 4.5 years. The protocol, study objectives, and pretreatment demographic characteristics of the group are summarized in this report, which is the first in a series in this i...
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::As cyclic 3',5'-guanosine monophosphate (cGMP) is still discussed as a possible mediator of the negative inotropic effects of cholinergic agents, the influence of acetylcholine (ACh) on force of contraction and cGMP tissue levels was studied in isolated, electrically driven guinea pig auricles in the presence of methy...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198611000-00009
更新日期:1986-11-01 00:00:00
abstract::At present, endothelin (ET) receptor classification remains controversial. We investigated the presence of atypical ETA receptors in human saphenous veins (SV). Human SV was obtained from 24 patients undergoing coronary artery bypass grafting. Vessels were set up in organ baths, stretched to a tension of 6 g, and left...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199800001-00049
更新日期:1998-01-01 00:00:00
abstract::Using selective endothelin (ET) receptor antagonists, we investigated which ET receptor subtypes mediate the changes in blood pressure and hematocrit produced by intraarterial injection of ET-1 in the anesthetized rabbit. In addition, the receptor through which ET-1 stimulates the release of prostacyclin (PGI2) and, h...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199322008-00050
更新日期:1993-01-01 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::The acute systemic and regional hemodynamic responses to a single oral dose (4 mg) of the angiotensin converting enzyme inhibitor perindopril were investigated in 10 patients with severe congestive heart failure. Perindopril produced significant and long-lasting decreases in systemic vascular resistance (-18%), right ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199004000-00002
更新日期:1990-04-01 00:00:00
abstract::Data are presented that define the risks of elevated blood pressure, both systolic and diastolic, and support the recent recommendations of the Third Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure in the United States that a consistently elevated pressure level above 140/90 mm ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-198507001-00020
更新日期:1985-01-01 00:00:00
abstract::The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. In addition to its well-established role in maintaining vascular homeostasis, the endothelium has been increasingly recogniz...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000469
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:Factor Xa (FXa) has been a target of considerable interest for drug development efforts aimed at suppressing thrombosis. In this report, a new orally active, small molecule, active-site directed FXa inhibitor, GW813893, has been profiled in a succession of in vitro and in vivo assays involved in its preclini...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31817e9b9e
更新日期:2008-07-01 00:00:00
abstract::The vasodilatory properties of prostacyclin were studied in 12 intubated patients who underwent coronary artery bypass surgery. When infused in doses of 2.5, 5, 10, and 20 ng/kg/min, prostacyclin produced a dose-dependent decrease in systemic vascular resistance from 2,702 +/- 143 to 1,654 +/- 106 dynes/cm5/m2 (p less...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198702000-00003
更新日期:1987-02-01 00:00:00
abstract::Histamine receptors are present in adrenergic terminals, and histamine is reported to inhibit release of the neurotransmitter norepinephrine (NE) at certain neuroeffector junctions. However, a physiological role for histamine in modifying adrenergic neurotransmission has not been established. To examine the interactio...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198705000-00012
更新日期:1987-05-01 00:00:00
abstract::Compound LY249933 and its component diastereomers, (RR) and (SR), were studied for their vascular and cardiac effects in vitro and in vivo. In guinea pig cardiac ventricular membranes, LY249933, (RR), and (SR) potently displaced bound [3H]nitrendipine (Kd values = 2-6 nM). In isolated guinea pig right ventricular stri...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::Endothelial cells and smooth muscle cells are the major cells that constitute blood vessels, and endothelial cells line the lumen of blood vessels. These 2 types of cells also play an integral role in the regional specialization of vascular structure. On the basis of these observations, we designed our study to invest...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31803e8756
更新日期:2007-05-01 00:00:00
abstract::Clopidogrel is metabolically activated by cytochrome P450 (CYP) isoenzymes. We evaluated whether St. John's wort (SJW), a CYP2C19 and CYP3A4 inducer, enhances the pharmacodynamic response of clopidogrel. Volunteers (n = 45) were screened for clopidogrel hyporesponsiveness after a 300-mg load. After a 7-day washout, hy...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/FJC.0b013e3181ffe8d0
更新日期:2011-01-01 00:00:00
abstract::Using the radioactive microsphere technique, we studied the acute systemic and regional hemodynamic effects of felodipine (10, 30, and 100 nmol/kg, i.v.) in conscious renal hypertensive rabbits. A dose-dependent decrease in arterial blood pressure was observed after felodipine administration, accompanied by tachycardi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198407000-00025
更新日期:1984-07-01 00:00:00
abstract::Cyclosporine (CsA) treatment in solid organ transplantation has represented one of the greatest advances in the past 20 years, reducing acute rejection and increasing long-term survival. However, CsA has an important side effect, producing renal vasoconstriction and systemic hypertension. The main histological finding...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-200000001-00002
更新日期:2000-01-01 00:00:00
abstract::Heart rate turbulence (HRT) denotes the baroreflex-mediated short-term oscillation of cardiac cycle lengths after spontaneous ventricular premature complexes. The physiological pattern of HRT consists of brief heart rate acceleration followed by more gradual heart rate deceleration before the heart rate returns to bas...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e3181d4c973
更新日期:2010-06-01 00:00:00
abstract::Phosphoinositide (PI) turnover, chronotropic and inotropic responses to alpha 1-adrenoceptor activation, and alpha 1-adrenoceptor density were studied in atria from rats with left ventricular myocardial infarction (LVMI) and noninfarcted rats. LVMI was produced after surgical ligation of the left coronary artery in 8-...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199103000-00017
更新日期:1991-03-01 00:00:00
abstract::Loop diuretics could adversely influence prognosis due to activation of neurohumoral mechanism in the long term. Previous study showed torasemide, a loop diuretic with anti-aldosteronergic properties, was associated with lower mortality in patients with chronic heart failure (CHF). We evaluated the effects of torasemi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/FJC.0b013e3181a717f7
更新日期:2009-06-01 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::Nonsedating H1-receptor antagonists appear to have wide and variable effects on the QT interval, mediated through modulation of cardiac K+ channels. By using the whole-cell patch-clamp technique, we examined the effects of terfenadine, loratadine, and descarboethoxyloratadine on a large family of K+ channels in ventri...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199707000-00007
更新日期:1997-07-01 00:00:00
abstract::Enhanced renin-angiotensin activity causes hypertension and cardiac hypertrophy. The angiotensin (Ang)-converting enzyme (ACE)2/Ang(1-7)/Mas axis pathway functions against Ang II type 1 receptor (AT1R) signaling. We investigated whether olmesartan (Olm), an AT1R blocker, inhibits cardiac hypertrophy independently of b...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000374
更新日期:2016-06-01 00:00:00
abstract::The effects of short-term amiodarone and dronedarone treatments on action potential characteristics and arrhythmia (ventricular tachycardia ) induced by reperfusion after global low-flow ischemia were studied in rat hearts. The actions of amiodarone and SR on recovery of coronary flow and contractile function were als...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200110000-00002
更新日期:2001-10-01 00:00:00
abstract::A contribution by active vasodilation to the hypotensive effect of medroxalol was investigated in anesthetized dogs and reserpinized pithed rats. In anesthetized dogs, intravenous doses of medroxalol, which decreased blood pressure and heart rate, also produced a dose-related vasodilation in the isolated perfused grac...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198301000-00022
更新日期:1983-01-01 00:00:00
abstract::Coronary artery disease (CAD) is the major cause of death in hypertensive patients in Western populations and further efforts are required to determine how best to reduce its incidence. Large-scale placebo-controlled trials of blood pressure reduction could resolve the uncertainty about the effects of antihypertensive...
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::Transgenic mice are often used to study the physiologic role of a known gene. The design of experiments with transgenic mice usually does not take into account strain and sex differences, at least in isolated vessels. Therefore, we have compared the contractile response of isolated aortae and isolated pulmonary arteri...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000232062.80084.4f
更新日期:2006-07-01 00:00:00
abstract::Plasma homocysteine levels increase in humans treated with fibrates but the molecular mechanisms are unknown. The goal of the present study was to determine the mechanism of this increase using animal models. Firstly, an increase in homocysteine was observed in mice treated with fenofibrate irrespective of the genetic...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200403000-00017
更新日期:2004-03-01 00:00:00