Abstract:
:Poor compliance may be responsible for symptomatic decompensation or neurohormonal "escape" in patients with heart failure treated over the long term with angiotensin-converting enzyme-1 (ACEI) drugs. Serum ACE activity is a poor index of neurohormonal suppression or haemodynamic effect after ACE-inhibitor treatment. Serum ACE activity may, however, be a useful index of compliance with treatment, as serum ACE is sensitive to the presence of an ACE inhibitor in the blood. Sixteen normotensive male volunteers of known ACE genotype received 7 days of randomised, double-blind therapy on four occasions 2 weeks apart with lisinopril 20 mg (L) or matched placebo (P) to simulate (A) noncompliance (all P), (B) full compliance (all L), (C) partial compliance (L days, 1, 3, 6; P days, 2, 4, 5, 7), or (D) single dose (L day 7; P, 1-6). Supine (30 min) blood pressure (BP)/heart rate (HR), ACE, and angiotensins were measured on d7 before dose and 4-6 h after dose. Results are mean +/- 1 SD. BP showed the expected small decrease with active treatment on d7 (B or D) but not with placebo (A) or partial compliance (C). Prestudy serum ACE, despite a wide range (16-124 U/L), was reproducible within subjects [coefficient of variation (CV), 1.7%]. Serum ACE activity, before (41.9 +/- 30) and after (41 +/- 30) angiotensin (A) I or II, were unaffected by treatment (placebo A). Active treatment (B) resulted in very low serum ACE activity and d7 and a small further suppression after dosing (before, 3.9 +/- 4; after, 1.8 +/- 4). AI was elevated in this group with further elevation after dosing (before, 234 +/- 116; after, 551 +/- 250). AII was only modestly reduced from baseline and showed little further suppression after dosing (before, 7.8 +/- 4; after, 6.3 +/- 5). Partial compliance (C) showed low ACE but no reduction after treatment (before, 7 +/- 3; after, 7 +/- 4), an elevated AI but no dosing effect (before, 187 +/- 198; after, 200 +/- 151) and reduced AII but with no further dose suppression (before, 6.4 +/- 3.4; after, 7 +/- 4) induced increase in peptide (compared with B). Single-dose treatment (D) showed ACE inhibition as expected (before, 47 +/- 30; after, 2.2 +/- 3). There was a dosing-related increase of AI but to a lesser extent than seen with chronic active dosing (B) (before, 39 +/- 10; after, 240 +/- 200). In contrast to long-term dosing, there was marked ANG II suppression (before, 8.8 +/- 4; after, 2.9 +/- 3). With this long-acting ACEI in a dose relevant to congestive heart failure management, we suggest that 4-6 h after-dosing serum ACE (< 5 EU/L) and elevated ANG I (> 300 pg/ml) can be used to confirm compliance with treatment. These absolute values may be altered in patients treated concomitant with loop diuretics. In principle, however, this may be a useful tool in clinical trials or in clinical practice after further work has been done to assess the limits in patients across the doses and across the range of available drugs used.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
MacFadyen RJ,Struthers ADdoi
10.1097/00005344-199701000-00018subject
Has Abstractpub_date
1997-01-01 00:00:00pages
119-24issue
1eissn
0160-2446issn
1533-4023journal_volume
29pub_type
临床试验,杂志文章,随机对照试验abstract::Bethanidine sulfate is a congener of bretylium tosylate, which has been reported to have antiarrhythmic and antifibrillatory effects. We studied the effects of bethanidine on transmembrane potentials recorded from canine Purkinje fibers and ventricular muscle cells, using standard microelectrode techniques. Normal Pur...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198501000-00009
更新日期:1985-01-01 00:00:00
abstract:OBJECTIVES:To identify and quantify the stimulatory and inhibitory activity of endothelial factors on Arginine vasopressin (AVP)-induced contractions. METHODS:In a standard organ bath set-up for isometric force recording, rabbit isolated renal artery rings were exposed to cumulative concentrations of AVP. Experiments ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200312000-00002
更新日期:2003-12-01 00:00:00
abstract::The aim of this study was to determine whether tumor necrosis factor (TNF)-alpha would impair basal and stimulated endothelium-dependent vasomotion in human resistance vessel. Changes in baseline and acetylcholine (ACh)-induced forearm vascular resistance (FVR) were measured plethysmographically before and after a low...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-200010000-00011
更新日期:2000-10-01 00:00:00
abstract::Clinical trials in patients with congestive heart failure have shown a wide disparity in the hemodynamic responses to chronic therapy with newer positive inotropic drugs. Therefore, the long-term efficacy of enoximone was studied in 10 patients with severe congestive heart failure. Patients were evaluated clinically, ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::Chronic diabetes mellitus finally leads to serious vascular dysfunction. Diosgenin is a natural steroidal saponin with potential cardiovascular protective effect. In this study, the protective effect of diosgenin was checked on the aorta from streptozotocin-induced diabetic rats. Diabetic rats received diosgenin (40 m...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000308
更新日期:2015-12-01 00:00:00
abstract::Tetrahydrobiopterin is the reduced unconjugated pterin that serves as an essential cofactor for the normal enzymatic function of the aromatic amino acid hydroxylases and for the nitric oxide synthases (NOS). Its role in the latter biochemistry is being increasing appreciated, as depletion or oxidation of BH4 results i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e318123f854
更新日期:2007-09-01 00:00:00
abstract::Left coronary artery ligations or sham operations were performed on pentobarbitone-anesthetized rats. The rats were sacrificed at various times after artery occlusion or sham operation and the creatine kinase (CK), potassium (K+), and noradrenaline (NA) content was determined in the left and right ventricular myocardi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1981-07-01 00:00:00
abstract::Protein kinase C (PKC) isoforms improve endothelial nitric oxide synthase activity and contractile Ca sensitivity in blood vessels. These actions may have opposite effects on propofol-induced vasodilation. This study examines the hypothesis that propofol induces relaxation by enhancing the PKC-mediated nitric oxide sy...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000275
更新日期:2015-09-01 00:00:00
abstract::The complementary antihypertensive effects of the beta-blocker/calcium antagonist combination has to be weighed against their additive and potentially detrimental negative inotropic, chronotropic, and dromotropic effects inherent in both classes of drugs. We reviewed the main adversity, particularly electrophysiologic...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198507004-00008
更新日期:1985-01-01 00:00:00
abstract::Phosphatidylinositol 4,5-bisphosphate hydrolysis at the plasma membrane by phospholipase C is one of the major hormone regulated intracellular signaling systems. The system generates the diffusible second messenger IP3 and the membrane bound messenger diacylglycerol. Spatial regulation of this system has been thought ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000195
更新日期:2015-03-01 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::The positive inotropic effect of DPI 201-106 has been studied in isolated, electrically driven papillary muscles of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WK). The positive inotropic effect of isoprenaline (Iso) and Ca2+ was studied for comparison. The maximal positive inotropic effect of Iso was...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198804000-00012
更新日期:1988-04-01 00:00:00
abstract::Increased sodium absorption in the gut is one mechanism contributing to hypertensive blood pressure values. The sodium-proton-exchanger subtype 3 (NHE3) is an important mediator of intestinal sodium absorption. The compound SAR is a new specific NHE3 inhibitor with extremely low oral absorbability leading to decreased...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000336
更新日期:2016-03-01 00:00:00
abstract::We investigated the endothelin (ET) receptors involved in the vasoconstrictor responses to ET-1 in rat pulmonary arteries and arterioles and the effect of endothelium removal, nitric oxide (NO) synthase inhibition, and hypoxia on ET-1-induced responses in the arteries. In isolated rat pulmonary artery rings (2-3 mm ID...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199405000-00022
更新日期:1994-05-01 00:00:00
abstract::We studied the acute effects of transmitter release induced by intracisternal (i.c.) 6-hydroxydopamine (6-OHDA) from mainly noradrenergic (NA) neurons and by 5,6-dihydroxytryptamine (5,6-DHT) from serotonergic (5HT) neurons. Each group of neurons affects blood pressure and heart rate in conscious rabbits through both ...
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::Flosequinan, a new orally active vasodilator, and its sulfone metabolite were evaluated for inotropic activity in isolated ferret papillary muscles and pentobarbital anesthetized open-chest dogs. In vitro, flosequinan and its sulfone derivative increased tension development in a concentration-dependent manner (1-50 mi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198909000-00009
更新日期:1989-09-01 00:00:00
abstract::PPARgamma agonists ameliorate insulin resistance and lower blood pressure. Volume expansion/edema has been observed in susceptible patients treated with these agents. Alterations of renal hemodynamics affect renal tubular reabsorption, and thus may contribute to volume expansion. This study seeks to determine whether ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200309000-00016
更新日期:2003-09-01 00:00:00
abstract::Glycogen synthase kinase (GSK)-3beta inhibitors play an anti-inflammatory role in several inflammatory diseases. Recent studies have demonstrated that GSK-3beta inhibitors protect against myocardial ischemia-reperfusion injury. However, the precise mechanisms remain unclear. We aimed to investigate the roles of inflam...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318186a84d
更新日期:2008-09-01 00:00:00
abstract::The mechanisms of sustained ventricular tachycardia (VT) induced by large cumulative dose of cesium chloride (Cs) remains unclear. Seven anesthetized rabbits were intravenously injected with Cs (1 mmol/kg) 3 times at 20-min intervals. The surface ECG and monophasic action potential of the left ventricular endocardium ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199805000-00009
更新日期:1998-05-01 00:00:00
abstract::The acute effects of doxorubicin on coronary perfusion and left ventricular pressures and intracellular phosphate metabolite levels, the latter obtained by 31P nuclear magnetic resonance, were measured simultaneously in isolated, isovolumic rat hearts (Langendorf preparation) perfused at constant flow. Nineteen experi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract::The oral anticoagulant edoxaban, a factor Xa inhibitor, will likely be coadministered with digoxin in some patients with atrial fibrillation. Both drugs are substrates for P-glycoprotein. The objective of this phase 1, parallel study was to assess the effects of coadministration of both drugs on their respective pharm...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/FJC.0b013e31826265b6.
更新日期:2012-10-01 00:00:00
abstract::Low density lipoprotein (LDL) oxidation plays a crucial role in the development and progression of atherosclerosis and is enhanced in patients with essential hypertension. This finding has stimulated a search for antihypertensive drugs with high intrinsic antioxidant properties. We investigated the antihypertensive an...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-199604000-00012
更新日期:1996-04-01 00:00:00
abstract::This study investigated the role of perivascular adipose tissue (PVAT) in the beneficial effects of andrographolide on vascular reactivity in endotoxaemic rats. After being challenged by lipopolysaccharide (4 mg/kg intraperitoneally), the rats were treated with andrographolide (1 mg/kg intraperitoneally). The response...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31829497ea
更新日期:2013-08-01 00:00:00
abstract::The possible relevance of intrinsic sympathomimetic activity (ISA) for beta-blocker-induced changes in plasma lipids was investigated by reviewing the literature and analyzing the results separately for nonselective beta-blockers, beta 1-selective beta-blockers, and those possessing ISA. It was confirmed that with the...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198300051-00008
更新日期:1983-01-01 00:00:00
abstract::Because the role of sodium channels in the initiation and maintenance of VF is not fully elucidated, we studied the significance of sodium channel activity in VF using sodium channel blockers. In nonischemic isolated feline hearts, the following electrophysiologic parameters were measured before and after application ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200012000-00015
更新日期:2000-12-01 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::Amlodipine, a new long-acting dihydropyridine calcium antagonist, was compared with hydrochlorothiazie (HCTZ) in 145 patients with mild to moderate hypertension. After 4 weeks of single-blind placebo runin, patients were randomly allocated to receive amlodipine (2.5-10 mg once daily, n = 97) or HCTZ (25-100 mg once da...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198812007-00022
更新日期:1988-01-01 00:00:00
abstract::The presence of endothelin (ET) receptors and the nature of the subtype and expression of ET were investigated in the human megakaryoblastic cell line MEG-01. By the RT-PCR procedure, we have shown that both ETA and ETB receptor subtype mRNAs are expressed in the cells. However, binding experiments have shown that the...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 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::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