Abstract:
:The short half-life, low plasma concentrations, and extensive biotransformation of prazosin suggest that it might be subject to extensive first-pass metabolism. Bioavailability, disposition, and hepatic extraction were studied in the dog. In conscious dogs whole blood prazosin concentrations were measured after oral and intravenous administration of the drug. Anesthetized dogs were used to measure prazosin concentrations in arterial and hepatic venous blood samples drawn simultaneously. The bioavailability of prazosin was 0.38 +/- 0.11. In anesthetized dogs the hepatic extraction of prazosin was 0.47 +/- 0.08 for a predicted availability of 0.53 +/- 0.08. Pharmacokinetic parameters were similar in conscious and anesthetized animals. Following intravenous administration to conscious dogs, prazosin concentrations in whole blood declined with a fast half-life of 3.9 +/- 1.74 min and a slow half-life of 153 +/- 24 min, the volume of distribution at steady state being 48.6 +/- 15.3 liters in dogs (mean weight, 22.6 kg). We conclude that prazosin availability following oral administration is low and that first-pass hepatic metabolism is largely responsible for this. A one-compartment model adequately describes prazosin pharmacokinetics in the dog.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Rubin P,Yee YG,Anderson M,Blaschke Tdoi
10.1097/00005344-197911000-00005subject
Has Abstractpub_date
1979-11-01 00:00:00pages
641-7issue
6eissn
0160-2446issn
1533-4023journal_volume
1pub_type
杂志文章abstract::This study was undertaken to determine and confer the cardioprotective effects of the adenosine A2 receptor (A2AR) and its impact on myocardial autophagy in the setting of reperfusion. We established a rat ischemia model by subjecting rats to 30 minutes of ischemia (I) and 120 minutes of reperfusion (R). The A2AR agon...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000239
更新日期:2015-07-01 00:00:00
abstract::Abdominal aortic aneurysms (AAA) is a multifactorial vascular disease with a high rate of mortality and brings heavy burden to both human and society. The pathological process behind AAA is complex. Elastin degradation, chronic inflammation, and vascular smooth muscle cell phenotypic modulation are involved in AAA for...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000785
更新日期:2020-03-01 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::No single pathophysiologic mechanism explains adequately cold-induced vasospasm in all forms of Raynaud's phenomenon. Local serotonin release from activated platelets is a contributory element in those disorders typified by structural arterial change, e.g., systemic sclerosis (scleroderma). Selective antagonism of S2-...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,评审
doi:
更新日期:1985-01-01 00:00:00
abstract::We have previously reported that production of endothelin (ET)-1 is markedly increased in failing hearts of rats with chronic heart failure (CHF). It was also reported that the production of angiotensin II (Ang II) is increased in the failing heart. In this study we investigated both converting enzymes of the ET-1 sys...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199800001-00119
更新日期:1998-01-01 00:00:00
abstract::The present study was undertaken to investigate the interaction between endothelin-1 (ET-1) and norepinephrine (NE) on contractile regulation in dog ventricular myocardium. ET-1 alone did not elicit any inotropic response in isolated dog ventricular trabeculae (37 degrees C, 0.5 Hz). In the presence of NE at a high co...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200000006-00004
更新日期:2000-01-01 00:00:00
abstract::In the absence of formal clinical trials, the efficacy of thiazide diuretics in patients with renal impairment remains in doubt. Our study was therefore designed to evaluate the separate and combined effects of single and multiple doses of hydrochlorothiazide (HCTZ) and furosemide (FU) on the glomerular filtration rat...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199509000-00008
更新日期:1995-09-01 00:00:00
abstract::Ranolazine was previously shown to stimulate cardiac glucose oxidation. Dichloroacetate (DCA) also does and was shown to improve exercise capacity in animals, but it has long-term toxicity problems. To test the hypothesis that ranolazine would increase exercise performance in the chronic heart failure (CHF) condition,...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199609000-00002
更新日期:1996-09-01 00:00:00
abstract::Using micropuncture techniques in euvolemic adult male Munich-Wistar rats, we assessed the functional role of renal beta-adrenoceptors in mediating neural control of glomerular filtration and proximal tubular reabsorption. The determinants of nephron filtration and rate of proximal tubular reabsorption were measured i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199103000-00007
更新日期:1991-03-01 00:00:00
abstract:OBJECTIVE:This study was designed to assess whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could prevent the recurrence of atrial fibrillation (AF). METHODS:A systemic literature search of PubMed, EMBASE, and Cochrane Controlled Trials Register till 2012 was performed...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1097/FJC.0b013e3182a094a1
更新日期:2013-10-01 00:00:00
abstract::Perturbations of the trans-sarcolemmal and sarcoplasmic Ca2+ transport contribute to the abnormal myocardial activity provoked by anoxia and reoxygenation. Whether Ca2+ pools of the extracellular compartment and sarcoplasmic reticulum (SR) are involved to the same extent in the dysfunction of the anoxic-reoxygenated i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199802000-00004
更新日期:1998-02-01 00:00:00
abstract::Desethylamiodarone (DA) is a major metabolite of amiodarone (AM), a Class III antiarrhythmic drug. The plasma pharmacokinetics and tissue distribution of AM and DA (10 mg/kg i.v.) were compared in anesthetized dogs. Plasma, white blood cell (WBC), red blood cell (RBC), liver, and skeletal muscle samples were obtained ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198710000-00002
更新日期:1987-10-01 00:00:00
abstract::Gangliosides, sialic acid-containing glycosphigolipids, are localized mostly to the outer leaflet of the lipid bilayer in the plasma membrane, particularly in brain. Gangliosides reduce edema formation, restore glucose metabolism, and increase cerebral blood flow after focal ischemia in the rat brain. We wished to det...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199307000-00013
更新日期:1993-07-01 00:00:00
abstract::The pharmacokinetics of losartan and EXP3174, an active metabolite of losartan, were evaluated in the anesthetized pig after both a single intravenous dose (3 mg/kg) and during constant intravenous infusion. The pharmacodynamic activities of losartan and EXP3174 were determined during constant intravenous infusion as ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199711000-00008
更新日期:1997-11-01 00:00:00
abstract::Epoxyeicosatrienoic acids, substrates for soluble epoxide hydrolase (sEH), exhibit vasodilatory and antihypertrophic activities. Inhibitors of sEH might therefore hold promise as heart failure therapeutics. We examined the ability of sEH inhibitors GSK2188931 and GSK2256294 to modulate cardiac hypertrophy, fibrosis, a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31827fe59c
更新日期:2013-04-01 00:00:00
abstract::Although the importance of adenosine (Ado)-receptor activation in preconditioning (PC) has been established, it is unclear whether cardioprotection afforded by PC is determined by the Ado level during PC ischemia or by that during sustained ischemia. Accordingly, we tested whether the PC effect is modified by augmenti...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199801000-00001
更新日期:1998-01-01 00:00:00
abstract::Spirapril (SCH 33844; 7-N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-(S)-alanyl-1,4-dithia- 7-azaspiro[4,4]-nonane-8(S)-carboxylic acid) is a new angiotensin-converting enzyme (ACE) inhibitor. SCH 33844 diacid inhibited hydrolysis of hip-his-leu by rabbit lung ACE in a potent (Ki = 0.74 nM), selective, and noncompetitive fa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198706107-00020
更新日期:1987-01-01 00:00:00
abstract::To investigate the pathophysiologic role(s) of endothelin-1 (ET-1) in pulmonary hypertension, we studied the expression of ETB-receptor mRNA in the lung and venous plasma concentrations of ET-1 in rats with monocrotaline-induced pulmonary hypertension (PH). Three weeks after s.c. injection of monocrotaline (60 mg/kg),...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199322008-00088
更新日期:1993-01-01 00:00:00
abstract::Amylin is a 37-amino acid peptide that shares considerable homology with calcitonin gene-related peptide (CGRP). Both peptides exert glycoregulatory actions and produce vasodilation of the cardiovascular system. We wished to determine if amylin exerts vasodilatory action in the perfused mesenteric arterial bed in a ma...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199512000-00012
更新日期:1995-12-01 00:00:00
abstract::The role of endothelin-B (ETB) receptor in partial ablation-induced chronic renal failure was evaluated using the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the ETB receptor gene. After 5/6 nephrectomy in ETB-deficient homozygous and wild-type (+/+) rats, we measured the systolic blood p...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000166316.45882.94
更新日期:2004-11-01 00:00:00
abstract::This study investigated whether glibenclamide exerts a defibrillatory action and if this action is mediated by a blockade of ATP-sensitive K+ channels (K(ATP)) or by an anti-free radical mechanism. Aerobically perfused isolated rat hearts were subjected to 10 min of pacing-induced ventricular fibrillation (VF) followe...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200306000-00013
更新日期:2003-06-01 00:00:00
abstract::beta-Adrenoceptor antagonists such as propranolol and atenolol ameliorate the symptoms of human hyperthyroidism. We wished to define whether the cardiac changes of hyperthyroidism are attenuated by treatment with the beta-adrenoceptor antagonist atenolol. Rats were treated with triiodothyronine (T3) [1 mg/kg/day subcu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::We compared platelet function results obtained with the VerifyNow P2Y12 (VN-P2Y12) point-of-care device and the light transmission aggregometry (5 and 20 microM adenosine diphosphate) method using an integrated database of eight clinical trials with a total of 591 subjects. The study was performed in healthy subjects,...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181dd0ec2
更新日期:2010-07-01 00:00:00
abstract::In anesthetized and ventilated guinea pigs, intravenous injection of ET-1, ET-2, or ET-3 induced similar rapid and dose-related increases in pulmonary inflation pressure (PIP) and mean arterial blood pressure (MABP). Indomethacin inhibited the increase in PIP evoked by ET-1, ET-2, or ET-3, whereas the changes in MABP ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00093
更新日期:1991-01-01 00:00:00
abstract::Ambulatory blood pressure monitoring (ABPM) is a particularly useful method for evaluating the effects of antihypertensive drugs. ABPM allows the therapeutic effect of an agent to be assessed continually by a large number of measurements, and the greater number of readings contributes to the higher degree of reproduci...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Coronary heart disease secondary to atherosclerosis is the leading cause of death for men in the United States. Using a new, nontransgenic, non-fat-fed mouse model of hyperlipidemia and atherosclerosis developed in our laboratory, we investigated the effect of sex on lipid profiles and subsequent aortic atheroscleroti...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200203000-00012
更新日期:2002-03-01 00:00:00
abstract::Clobutinol has been clinically reported to induce long QT syndrome. To clarify its cardiac electrophysiological properties, we compared effects of clobutinol on the isolated myocardium and anesthetized guinea pig heart with those of a hERG K channel blocker, E-4031. In isolated guinea pig ventricular tissues, clobutin...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181bfb17c
更新日期:2009-12-01 00:00:00
abstract::Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced by endothelial cells of blood vessels. This peptide has quite a unique structure and pharmacological properties. ET-1 is produced in endothelial cells and may be secreted in a similar way to some paracrine hormones. The pressor response of ET-1 is large...
journal_title:Journal of cardiovascular pharmacology
pub_type: 历史文章,杂志文章,评审
doi:10.1097/00005344-198900135-00002
更新日期:1989-01-01 00:00:00
abstract::Death during and following myocardial infarction can arise from a number of different causes. Some of them, such as early ventricular fibrillation and cardiac rupture, seem unrelated to infarct size. However, deaths occurring later during the course of infarction do seem to be related to the extent of myocardial damag...
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::Data of 52 patients, 29 women and 23 men aged 32-68 years (mean age 47 years) with essential hypertension, participating in three open therapeutic trials with either enalapril, lisinopril, or perindopril were evaluated to assess the effects of angiotensin-converting enzyme (ACE) inhibition on glucose and lipid metabol...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-199401000-00010
更新日期:1994-01-01 00:00:00