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 fashion. SCH 33844 (0.03-1 mg/kg p.o.) produced dose-related inhibition of angiotensin I (AI) pressor responses in conscious rats with a duration of 24 h at the higher dose. SCH 33844 (0.3-30 mg/kg p.o.) reduced blood pressure in a dose-related manner in conscious SHR with a 24-h duration. Antihypertensive activity was enhanced in the presence of hydrochlorothiazide. The drug (1-10 mg/kg p.o.) also lowered blood pressure in conscious hydrochlorothiazide-treated normotensive dogs. In anesthetized dogs, SCH 33844 (1 mg/kg i.v.) reduced blood pressure and total peripheral vascular resistance and slightly increased cardiac output and stroke volume. These results suggest that peripheral vasodilation is the primary mechanism of the antihypertensive action. The metabolic profile of SCH 33844 was evaluated in dogs and rats. The compound was absorbed in a dose-proportional manner and excreted primarily as the diacid form. In contrast to captopril and enalapril, most of the drug (67%) was excreted into the feces following i.v. dosing. Chronic toxicological evaluation in dogs and rats demonstrated that the drug was relatively devoid of toxicity at oral doses as high as 400 and 450 mg/kg/day, respectively. Slight decreases in heart weight (rats) and increases in granularity of the juxtaglomerular apparatus were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Sybertz EJ,Watkins RW,Ahn HS,Baum T,La Rocca P,Patrick J,Leitz Fdoi
10.1097/00005344-198706107-00020subject
Has Abstractpub_date
1987-01-01 00:00:00pages
S105-8eissn
0160-2446issn
1533-4023journal_volume
10 Suppl 7pub_type
杂志文章abstract::Monophasic action potentials (MAPs) were utilized to examine the basis for cesium-induced arrhythmia in the dog. Cesium chloride (1 mmol/kg i.v.) produced an immediate prolongation of MAP (250 +/- 11 to 396 +/- 34 ms, p less than 0.05). Coupled premature ventricular beats (345 +/- 46 ms) and polymorphic ventricular ta...
journal_title:Journal of cardiovascular pharmacology
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abstract::MDL 19205 4-ethyl-1-,3-dihydro-5-(4-pyridinylcarbonyl)-2H-imidazol-2-one, a new cardioactive agent, has been shown to increase myocardial contractile force in animals. It is effective by both oral and intravenous routes. We studied 11 patients with congestive heart failure--in 10 cases owing to coronary artery disease...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198702000-00013
更新日期:1987-02-01 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::Calcium entry blockers seem useful for energy conservation in the ischemic heart. Their exact mechanism of action, however, remains uncertain. In this study we investigated the effect of 30 nM nisoldipine on carbohydrate metabolism in isolated rat heart perfused with glucose-containing medium. Nisoldipine increased fl...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198505000-00013
更新日期:1985-05-01 00:00:00
abstract::The long QT-related arrhythmia torsades de pointes (TdP) can arise with mutations in HERG and during treatment with drugs that block cardiac I Kr, the current encoded by HERG. Multiple test systems have been used to assess drug block of I Kr. This study evaluated the I Kr blocking potency of a series of antiarrhythmic...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200111000-00010
更新日期:2001-11-01 00:00:00
abstract::Diabetes is a devastating disease with multiple adverse effects on the vasculature. Moreover, hypertension is a prerequisite for patients with diabetes to progress to end-stage renal disease and to develop cardiovascular complications. Adequate control of blood glucose and blood pressure are the two most important fac...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199800002-00006
更新日期:1998-01-01 00:00:00
abstract::Low doses of ethanol can produce negative functional effects in ventricular myocytes. This may be related to the nitric oxide-cyclic GMP signal transduction system. We tested the hypothesis that ethanol stimulated endothelial nitric oxide synthase and this caused the negative functional effects in cardiac myocytes. Th...
journal_title:Journal of cardiovascular pharmacology
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更新日期:2005-09-01 00:00:00
abstract::Electrophysiologic properties of surviving Purkinje cardiomyocytes in the late postmyocardial-infarction phase are not well established. By using standard microelectrode techniques, we evaluated the effects of the class III agent d-sotalol on action potential parameters of single Purkinje cardiomyocytes isolated from ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199808000-00015
更新日期:1998-08-01 00:00:00
abstract::To explore endothelium-dependent relaxation and the L-arginine (L-ARG)-nitric oxide (NO) pathway during chronic hypoxia, we examined isolated rings from large conduit pulmonary arteries and aorta from rats exposed to either room air (N), 3-week hypoxia (H), or 3-week H followed by 72-h recovery to normoxia (room air)....
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199312000-00018
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abstract::Several antiarrhythmic agents with Na-channel blocking action have been shown to inhibit cardiac K(ATP) channels. We used cibenzoline to examine its precise target site using patch-clamp techniques and receptor binding assays in guinea-pig ventricular myocytes. Exposure of myocytes to a glucose-free perfusate containi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200003000-00014
更新日期:2000-03-01 00:00:00
abstract::The sensitivity of smooth muscle from aortas of spontaneously hypertensive rats (SHR), renal hypertensive rats: two kidney-one clip and one kidney-one clip (2K-1C, 1K-1C) and DOCA salt hypertensive rats to the relaxant effect of nifedipine (NIF) was studied. A parallel leftward shift of the concentration-relaxation cu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198609000-00005
更新日期:1986-09-01 00:00:00
abstract::Fifteen patients with stable angina participated in a 12-week crossover study to evaluate the efficacy of nifedipine and nitroglycerin patches. There was an initial 2-week drug washout period followed by a 2-week control period when patients received no other antianginal treatment other than sublingual nitroglycerin f...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198709000-00010
更新日期:1987-09-01 00:00:00
abstract::Vasopeptidase inhibitors are single molecules that inhibit neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) simultaneously. Omapatrilat, the first in this new class of cardiovascular agents, potentiates vasodilatory and cardioprotective peptides and represses angiotensin II. This study compared the ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199912000-00003
更新日期:1999-12-01 00:00:00
abstract::MDL 17,043 (1,3-dihydro-4-methyl-5-[4-(methylthio)-benzoyl]-2H-imidazol-2-one) is a new drug with cardiotonic properties. Its effects on several biochemical systems considered to be important in myocardial contraction were investigated and compared with those produced by amrinone and theophylline. Dog cardiac phosphod...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198205000-00024
更新日期:1982-05-01 00:00:00
abstract::A randomized, double-blind, crossover trial was carried out in 17 hypertensive patients to evaluate the hypotensive efficacy and safety of verapamil. Verapamil in doses of 120 mg thrice daily was compared with pindolol in doses of 7.5 mg twice daily. A thiazide diuretic was given with both drugs. Blood pressure fell a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198103000-00007
更新日期:1981-03-01 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::Dilevalol, the stereoisomer of labetalol, was given in repeated incremental intravenous bolus injections to 10 patients with severe hypertension requiring urgent blood pressure lowering. The mean cumulative dose of dilevalol was 445 +/- 165 mg. Blood pressure was reduced from 201 +/- 33/131 +/- 13 to 150 +/- 12/109 +/...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-05-01 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...
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abstract::Structurally and pharmacologically diverse vasodilators are known to lower blood pressure, increase heart rate, and produce acute injury to right coronary arteries in the dog. Administration of low concentrations of endothelin-1 (ET-1) to anesthetized dogs causes coronary vasoconstriction and reductions in coronary bl...
journal_title:Journal of cardiovascular pharmacology
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更新日期:1998-01-01 00:00:00
abstract::Arrhythmias occur 24 h after occlusion of the left anterior descending (LAD) coronary artery in the canine heart and have been attributed to the abnormal spontaneous activity in subendocardial Purkinje fibers, which are markedly depolarized. The major current underlying normal automaticity in these fibers is i(f). Alt...
journal_title:Journal of cardiovascular pharmacology
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abstract::The pharmacologic properties of a novel nonpeptide endothelin (ET) receptor antagonist, S-1255 ([R]-[+]-2-[benzo(1,3)dioxol-5-yl]-6-isopropyl-4-[4-methoxyphenyl]-2H-chromene-3-carboxylic acid), was studied. [3H]S-1255 specifically bound to porcine aortic smooth muscle membranes expressing only ET(A) receptors with a K...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200104000-00014
更新日期:2001-04-01 00:00:00
abstract::Intracellular pH (pHi) regulation in the heart relies on the activity of three membrane mechanisms: the Na+/H+ exchange and an Na+, HCO3(-)-dependent transport, both activated after an acid load, and the Cl-/HCO(3-) exchange, activated by an intracellular alkalinization. Whereas several specific inhibitors of Na+/H+ e...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199610000-00011
更新日期:1996-10-01 00:00:00
abstract::To assess dose-related effects of enalapril, we treated eight hospitalized hypertensive patients receiving constant sodium intake with incremental doses of this new angiotensin converting-enzyme blocking drug. After a few days of placebo treatment, enalapril was given in single daily doses, starting with 1.25 mg and i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198600081-00006
更新日期:1986-01-01 00:00:00
abstract::We studied the influence of dietary L-arginine (L-ARG) supplementation on forearm resistance arteries in vivo and the effect of exogenous addition of L-ARG to subcutaneous arteries isolated from gluteal biopsies. Twenty-six healthy males were recruited, and 16 were randomly allocated in a double-blind protocol to rece...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1996-07-01 00:00:00
abstract::Erythrocyte lithium-sodium countertransport, a mode of ouabain-insensitive monovalent cation metabolism, is increased in human essential hypertension, but no pathophysiological link to hypertension has yet been established. Similarities between red cell lithium-sodium countertransport and renal proximal tubular sodium...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198608005-00015
更新日期:1986-01-01 00:00:00
abstract::Both in the periphery and in the central nervous system, alpha-adrenoceptors can be subdivided into alpha 1-types. alpha 1-Receptors are sensitive to low concentrations of the agonists phenylephrine and methoxamine, and of the antagonists corynanthine and prazosin. alpha 1-Receptors are sensitive to low concentrations...
journal_title:Journal of cardiovascular pharmacology
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doi:10.1097/00005344-198200041-00002
更新日期:1982-01-01 00:00:00
abstract::Mikania laevigata, popularly known in Brazil as guaco, is widely used for respiratory disorders. As this plant is rich in coumarins, there is evidence of indications that it may cause bleeding and therefore should not be used concomitantly with anticoagulants. The basis of this information is very theoretical, with no...
journal_title:Journal of cardiovascular pharmacology
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abstract::Buchang NaoXinTong (NXT) is a Chinese medicine that has been used for many years for treatment of patients with coronary heart disease (CHD) in China. Statins substantially reduce hypercholesterolemia and CHD mortality and morbidity. However, there is still a lot of CHD patients who do not respond well to statin thera...
journal_title:Journal of cardiovascular pharmacology
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abstract::An acetylcholinesterase inhibitor (donepezil hydrochloride) has recently been used for the treatment of senile dementia of Alzheimer type. The effect of this acetylcholinesterase inhibitor on the autonomic nervous control of the heart was investigated in 17 patients with senile dementia of Alzheimer type. Donepezil ad...
journal_title:Journal of cardiovascular pharmacology
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更新日期:2003-01-01 00:00:00
abstract::Interventions that inhibit neutrophil infiltration into myocardial tissue after ischaemia and reperfusion are reported to reduce the size of the infarct. We examined whether administration of trimetazidine, which is reported to reduce myocardial infarct size, affects this process. [111In]Neutrophils and [125I]albumin ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199312000-00008
更新日期:1993-12-01 00:00:00